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Terms modified by SCN Selected AbstractsPowder second harmonic generation measurement and thermal decomposition mechanisms of a new organometallic compound [(18C6)Li][Cd(SCN)3]CRYSTAL RESEARCH AND TECHNOLOGY, Issue 9 2009J. J. Zhang Abstract Single crystals of a novel nonlinear optical organometallic compound CLTC, ([(18C6)Li][Cd(SCN)3]), were grown from aqueous solutions via evaporation technique and characterized by IR spectroscopy, thermal gravimetric analysis and X-ray single-crystal diffraction. By X-ray single-crystal structural analysis it is revealed that the compound crystallized in a noncentrosymmetric space group Cmc21 of orthorhombic system with cell parameter a = 14.767(3) Å, b = 15.454(3) Å, c = 10.644(2) Å, V = 2429.0(8) Å3 and Z = 4. The thermal stability and thermal decomposition of CLTC crystal were investigated by means of thermogravimetry and differential thermal analysis. The second harmonic generation (SHG) efficiency was measured using the Kurtz and Perry powder technique. It was shown that the value of the SHG efficiency of CLCT powder was about 2 times higher than that of potassium dihydrogen phosphate (KDP). (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Growth and properties of an organometallic nonlinear optical crystal: bis(isothiocyanato)-bis(4-methylpyridine)zinc(II) (Zn(SCN)2(C6H7N)2)CRYSTAL RESEARCH AND TECHNOLOGY, Issue 12 2006L. Y. Zhu Abstract Bis(isothiocyanato)-bis(4-methylpyridine)zinc(II)(Zn(SCN)2(C6H7N)2), (abbreviated as ZBNC) single crystals of optical quality have been grown from acetone solution by the slow temperature-lowering method. Its solubilities at different temperatures in acetone were measured. The X-ray powder diffraction (XRPD) spectroscopy of ZBNC crystal was performed at room temperature. The second harmonic generation (SHG) efficiency was determined by powder technique of Kurtz and Perry using Nd:YAG laser, which is equivalent to KDP crystal. The thermal decomposition process was characterized by thermal gravity and differential thermal analysis (TG\DTA). The specific heat of the crystal is 1440.67 J/mol·K at 325 K. The IR spectrum was recorded in the 500,3500 cm,1 region, using KBr pellets on a Nicolet 170sx FT-IR spectrometer. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Synthesis and X-ray structure of two conformational isomers of [Zn(medpt)(SCN)2], medpt = bis (3 , aminopropyl)methylamineCRYSTAL RESEARCH AND TECHNOLOGY, Issue 2 2006S. Guha Abstract Two conformational isomers of [Zn (medpt)(NCS)2], medpt=bis(3-aminopropyl) methylamine, (1) and (2) have been synthesised and the crystal structures are determined using single crystal X-ray diffraction. The structures of the complexes have been solved by Patterson method and refined by full-matrix least- squares techniques to R1 = 0.0524 for (1) and R1 = 0.0506 for (2), respectively. The geometry around the Zn(II) centre in both isomers is distorted trigonal bipyramidal. The two pendent thiocyanate moieties in (1), with Zn,N,C angles 167.9(4),173.9(4)º, coordinate the mental centre almost linearly while the corresponding coordinations in (2) are significantly bent [Zn,N,C angles 150.8(3),153.1(2)°]. Intermolecular N,H,S hydrogen bonds stabilise the crystal packing in the complexes forming infinite chains parallel to the [100] direction. The combinations of molecular chains generate three/two dimensional supramolecular framework in complexes (1) and (2). (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Aluminum(III) Porphyrins as Ionophores for Fluoride Selective Polymeric Membrane ElectrodesELECTROANALYSIS, Issue 6 2006Jeremy Abstract Aluminum(III) porphyrins are examined as potential fluoride selective ionophores in polymeric membrane type ion-selective electrodes. Membranes formulated with Al(III) tetraphenyl (TPP) or octaethyl (OEP) porphyrins are shown to exhibit enhanced potentiometric selectivity for fluoride over more lipophilic anions, including perchlorate and thiocyanate. However, such membrane electrodes display undesirable super-Nernstian behavior, with concomitant slow response and recovery times. By employing a sterically hindered Al(III) picket fence porphyrin (PFP) complex as the membrane active species, fully reversible and Nernstian response toward fluoride is achieved. This finding suggests that the super-Nernstian behavior observed with the nonpicket fence metalloporphyrins is due to the formation of aggregate porphyrin species (likely dimers) within the membrane phase. The steric hindrance of the PFP ligand structure eliminates such chemistry, thus leading to theoretical response slopes toward fluoride. Addition of lipophilic anionic sites into the organic membranes enhances response and selectivity, indicating that the Al(III) porphyrin ionophores function as charged carrier type ionophores. Optimized membranes formulated with Al(III)-PFP in an o -nitrophenyloctyl ether plasticized PVC film exhibit fast response to fluoride down to 40,,M, with very high selectivity over SCN,, ClO4,, Cl,, Br, and NO3, (kpot<10,3 for all anions tested). With further refinements in the membrane chemistry, it is anticipated that Al(III) porphyrin-based membrane electrodes can exhibit potentiometric fluoride response and selectivity that approaches that of the classical solid-state LaF3 crystal-based fluoride sensor. [source] Reactions of [Et4N][Tp*W(,3 -S)(,-S)2(CuSCN)2] with Nitrogen Donor Ligands: Syntheses, Structures, and Third-Order Nonlinear Optical PropertiesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 28 2009Zhen-Hong Wei Abstract Reactions of the preformed cluster [Et4N][Tp*W(,3 -S)(,-S)2(CuSCN)2] (1) with pyridine (py), 4,4,-bipyridine (4,4,-bipy), or 1,3-bis(4-pyridyl)propane (bpp) led to the formation of three neutral [Tp*W(,3 -S)(,-S)2Cu2]-based compounds [Tp*W(,3 -S)(,-S)2Cu2(SCN)(py)2] (2), [{Tp*W(,3 -S)(,-S)2Cu2(SCN)}2(4,4,-bipy)]·3.5H2O (3·3.5H2O), and [Tp*W(,3 -S)(,-S)2Cu2(SCN)(bpp)]2 (4), respectively. Compounds 2,4 were characterized by elemental analysis, IR spectra, UV/Vis spectra, 1H NMR, and X-ray analysis. There are two linkage isomers [Tp*W(,3 -S)(,-S)2Cu2(SCN)(py)2] and [Tp*W(,3 -S)(,-S)2Cu2(NCS)(py)2], each of which has its own enantiomeric pair in the crystal of 2. Compound 3 has a double butterfly-shaped structure in which two [Tp*W(,3 -S)(,-S)2Cu2(SCN)] fragments are linked with a single 4,4,-bipy bridge. For 4, the two butterfly-shaped [Tp*W(,3 -S)(,-S)2Cu2(SCN)] fragments are interconnected by a pair of bpp bridges. The third-order nonlinear optical (NLO) performances of 2,4 in DMF were also investigated by Z -scan techniques.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Anion-Directed Template Synthesis and Hydrolysis of Mono-Condensed Schiff Base of 1,3-Pentanediamine and o -Hydroxyacetophenone in NiII and CuII ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2008Pampa Mukherjee Abstract Bis(o -hydroxyacetophenone)nickel(II) dihydrate, on reaction with 1,3-pentanediamine, yields a bis-chelate complex [NiL2]·2H2O (1) of mono-condensed tridentate Schiff baseligand HL {2-[1-(3-aminopentylimino)ethyl]phenol}. The Schiff base has been freed from the complex by precipitating the NiII as a dimethylglyoximato complex. HL reacts smoothly with Ni(SCN)2·4H2O furnishing the complex [NiL(NCS)] (2) and with CuCl2·2H2O in the presence of NaN3 or NH4SCN producing [CuL(N3)]2 (3) or [CuL(NCS)] (4). On the other hand, upon reaction with Cu(ClO4)2·6H2O and Cu(NO3)2·3H2O, the Schiff base undergoes hydrolysis to yield ternary complexes [Cu(hap)(pn)(H2O)]ClO4 (5) and [Cu(hap)(pn)(H2O)]NO3 (6), respectively (Hhap = o -hydroxyacetophenone and pn = 1,3-pentanediamine). The ligand HL undergoes hydrolysis also on reaction with Ni(ClO4)2·6H2O or Ni(NO3)2·6H2O to yield [Ni(hap)2] (7). The structures of the complexes 2, 3, 5, 6, and 7 have been confirmed by single-crystal X-ray analysis. In complex 2, NiII possesses square-planar geometry, being coordinated by the tridentate mono-negative Schiff base, L and the isothiocyanate group. The coordination environment around CuII in complex 3 is very similar to that in complex 2 but here two units are joined together by end-on, axial-equatorial azide bridges to result in a dimer in which the geometry around CuII is square pyramidal. In both 5 and 6, the CuII atoms display the square-pyramidal environment; the equatorial sites being coordinated by the two amine groups of 1,3-pentanediamine and two oxygen atoms of o -hydroxyacetophenone. The axial site is coordinated by a water molecule. Complex 7 is a square-planar complex with the Ni atom bonded to four oxygen atoms from two hap moieties. The mononuclear units of 2 and dinuclear units of 3 are linked by strong hydrogen bonds to form a one-dimensional network. The mononuclear units of 5 and 6 are joined together to form a dimer by very strong hydrogen bonds through the coordinated water molecule. These dimers are further involved in hydrogen bonding with the respective counteranions to form 2-D net-like open frameworks. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] In Quest of the Double Rotaxane Formation of the Bis(coronand) (1,5),(2,4)-Durenetetrayl-bis(18-crown-5) with Organomagnesium CompoundsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 1 2004Gerard P. M. van Klink Abstract The interaction between the title compound, bis(coronand) 8,and the diarylmagnesium compounds Ph2Mg and (p - tBuC6H4)2Mg in diethyl ether leads to the formation of 1:2 complexes (9 and 10, respectively), irrespective of the initial ratio of the components. In [D8]toluene, the three complex types can be discerned by 1H NMR spectroscopy: double side-on (9a, 10a), side-on/rotaxane (9b, 10b), and, to a very minor extent, double rotaxane (9c, 10c). In the case of 10a and 10b, the temperature dependence showed that rotaxane formation is enthalpically favored at the expense of a more negative entropy. As crystals suitable for structure determination could not be obtained from 9 and 10, the interaction of 8 with the sterically less demanding Hg(SCN)2 was studied. In this case, analogous pseudorotaxanes are formed exclusively, and both the 1:2 complex [8·{Hg(SCN)2}2] (11) and its 1:1 analogue 12 were observed. The double rotaxane structure of 11 was confirmed by X-ray crystal structure determination. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Roles of light and serotonin in the regulation of gastrin-releasing peptide and arginine vasopressin output in the hamster SCN circadian clockEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jessica M. Francl Abstract Daily timing of the mammalian circadian clock of the suprachiasmatic nucleus (SCN) is regulated by photic input from the retina via the retinohypothalamic tract. This signaling is mediated by glutamate, which activates SCN retinorecipient units communicating to pacemaker cells in part through the release of gastrin-releasing peptide (GRP). Efferent signaling from the SCN involves another SCN-containing peptide, arginine vasopressin (AVP). Little is known regarding the mechanisms regulating these peptides, as literature on in vivo peptide release in the SCN is sparse. Here, microdialysis,radioimmunoassay procedures were used to characterize mechanisms controlling GRP and AVP release in the hamster SCN. In animals housed under a 14/10-h light,dark cycle both peptides exhibited daily fluctuations of release, with levels increasing during the morning to peak around midday. Under constant darkness, this pattern persisted for AVP, but rhythmicity was altered for GRP, characterized by a broad plateau throughout the subjective night and early subjective day. Neuronal release of the peptides was confirmed by their suppression with reverse-microdialysis perfusion of calcium blockers and stimulation with depolarizing agents. Reverse-microdialysis perfusion with the 5-HT1A,7 agonist 8-OH-DPAT ((±)-8-hydroxydipropylaminotetralin hydrobromide) during the day significantly suppressed GRP but had little effect on AVP. Also, perfusion with the glutamate agonist NMDA, or exposure to light at night, increased GRP but did not affect AVP. These analyses reveal distinct daily rhythms of SCN peptidergic activity, with GRP but not AVP release attenuated by serotonergic activation that inhibits photic phase-resetting, and activated by glutamatergic and photic stimulation that mediate this phase-resetting. [source] Tissue-type plasminogen activator-plasmin-BDNF modulate glutamate-induced phase-shifts of the mouse suprachiasmatic circadian clock in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Xiang Mou Abstract The mammalian circadian clock in the suprachiasmatic nucleus (SCN) maintains environmental synchrony through light signals transmitted by glutamate released from retinal ganglion terminals. Brain-derived neurotrophic factor (BDNF) is required for light/glutamate to reset the clock. In the hippocampus, BDNF is activated by the extracellular protease, plasmin, which is produced from plasminogen by tissue-type plasminogen activator (tPA). We provide data showing expression of proteins from the plasminogen activation cascade in the SCN and their involvement in circadian clock phase-resetting. Early night glutamate application to SCN-containing brain slices resets the circadian clock. Plasminogen activator inhibitor-1 (PAI-1) blocked these shifts in slices from wild-type mice but not mice lacking its stabilizing protein, vitronectin (VN). Plasmin, but not plasminogen, prevented inhibition by PAI-1. Both plasmin and active BDNF reversed ,2 -antiplasmin inhibition of glutamate-induced shifts. ,2 -Antiplasmin decreased the conversion of inactive to active BDNF in the SCN. Finally, both tPA and BDNF allowed daytime glutamate-induced phase-resetting. Together, these data are the first to demonstrate expression of these proteases in the SCN, their involvement in modulating photic phase-shifts, and their activation of BDNF in the SCN, a potential ,gating' mechanism for photic phase-resetting. These data also demonstrate a functional interaction between PAI-1 and VN in adult brain. Given the usual association of these proteins with the extracellular matrix, these data suggest new lines of investigation into the locations and processes modulating mammalian circadian clock phase-resetting. [source] Daily rhythms and sex differences in vasoactive intestinal polypeptide, VIPR2 receptor and arginine vasopressin mRNA in the suprachiasmatic nucleus of a diurnal rodent, Arvicanthis niloticusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009M. M. Mahoney Abstract Diurnal and nocturnal animals differ with respect to the time of day at which the ovulatory surge in luteinizing hormone occurs. In some species this is regulated by the suprachiasmatic nucleus (SCN), the primary circadian clock, via cells that contain vasoactive intestinal polypeptide (VIP) and vasopressin (AVP). Here, we evaluated the hypothesis that chronotype differences in the timing of the luteinizing hormone surge are associated with rhythms in expression of the genes that encode these neuropeptides. Diurnal grass rats (Arvicanthis niloticus) were housed in a 12/12-h light,dark cycle and killed at one of six times of day (Zeitgeber time 1, 5, 9, 13, 17, 21; ZT 0 = lights-on). In-situ hybridization was used to compare levels of vip, avp and VIP receptor mRNA (vipr2) in the SCN of intact females, ovariectomized females, ovariectomized females given estradiol and intact males. We found a sex difference in vip rhythms with a peak occurring at ZT 13 in males and ZT 5 in intact females. In all groups avp mRNA rhythms peaked during the day, from ZT 5 to ZT 9, and had a trough in the dark at ZT 21. There was a modest rhythm and sex difference in the pattern of vipr2. Most importantly, the patterns of each of these SCN rhythms relative to the light,dark cycle resembled those seen in nocturnal rodents. Chronotype differences in timing of neuroendocrine events associated with ovulation are thus likely to be generated downstream of the SCN. [source] Unpredictable feeding schedules unmask a system for daily resetting of behavioural and metabolic food entrainmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2007Carolina Escobar Abstract Restricted feeding schedules (RFS) are a potent Zeitgeber that uncouples daily metabolic and clock gene oscillations in peripheral tissues from the suprachiasmatic nucleus (SCN), which remains entrained to the light,dark cycle. Under RFS, animals develop food anticipatory activity (FAA), characterized by arousal and increased locomotion. Food availability in nature is not precise, which suggests that animals need to adjust their food-associated activity on a daily basis. This study explored the capacity of rats to adjust to variable and unpredictable feeding schedules. Rats were exposed either to RFS with fixed daily meal (RF) or to a variable meal time (VAR) during the light phase. RF and VAR rats exhibited daily metabolic oscillations driven by the last meal event; however, VAR rats were not able to show a robust adjustment in the anticipating corticosterone peak. VAR rats were unable to exhibit FAA but exhibited a daily activation pattern in phase with the previous meal. In both groups the dorsomedial nucleus of the hypothalamus and arcuate nucleus, involved in energy balance, exhibited increased c-Fos expression 24 h after the last meal, while only RF rats exhibited low c-Fos expression in the SCN. Data show that metabolic and behavioural food-entrained rhythms can be reset on a daily basis; the two conditions elicit a similar hypothalamic response, while only the SCN is inhibited in rats exhibiting anticipatory activity. The variable feeding strategy uncovered a rapid (24-h basis) resetting mechanism for metabolism and general behaviour. [source] Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Clare Guilding Abstract The suprachiasmatic nucleus of the hypothalamus (SCN) is the master circadian pacemaker or clock in the mammalian brain. Canonical theory holds that the output from this single, dominant clock is responsible for driving most daily rhythms in physiology and behaviour. However, important recent findings challenge this uniclock model and reveal clock-like activities in many neural and non-neural tissues. Thus, in addition to the SCN, a number of areas of the mammalian brain including the olfactory bulb, amygdala, lateral habenula and a variety of nuclei in the hypothalamus, express circadian rhythms in core clock gene expression, hormone output and electrical activity. This review examines the evidence for extra-SCN circadian oscillators in the mammalian brain and highlights some of the essential properties and key differences between brain oscillators. The demonstration of neural pacemakers outside the SCN has wide-ranging implications for models of the circadian system at a whole-organism level. [source] Diurnal regulation of the gastrin-releasing peptide receptor in the mouse circadian clockEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Ilia N. Karatsoreos Abstract In mammals, circadian rhythms are generated by the suprachiasmatic nuclei (SCN) of the hypothalamus. SCN neurons are heterogeneous and can be classified according to their function, anatomical connections, morphology and/or peptidergic identity. We focus here on gastrin-releasing peptide- (GRP) and on GRP receptor- (GRPr) expressing cells of the SCN. Pharmacological application of GRP in vivo or in vitro can shift the phase of circadian rhythms, and GRPr-deficient mice show blunted photic phase shifting. Given the in vivo and in vitro effects of GRP on circadian behavior and on SCN neuronal activity, we investigated whether the GRPr might be under circadian and/or diurnal control. Using in situ hybridization and autoradiographic receptor binding, we localized the GRPr in the mouse SCN and determined that GRP binding varies with time of day in animals housed in a light,dark cycle but not in conditions of constant darkness. The latter results were confirmed with Western blots of SCN tissue. Together, the present findings reveal that changes in GRPr are light driven and not endogenously organized. Diurnal variation in GRPr activity probably underlies intra-SCN signaling important for entrainment and phase shifting. [source] Blockade of the NPY Y5 receptor potentiates circadian responses to light: complementary in vivo and in vitro studiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2004P. C. Yannielli Abstract Neuropeptide Y (NPY) is delivered to the suprachiasmatic nuclei (SCN) circadian pacemaker via an input from the thalamic intergeniculate leaflet. NPY can inhibit light-induced responses of the circadian system of Syrian hamsters. Here we studied whether an antagonist to NPY receptors can be used to potentiate photic phase shifts late in the subjective night. First we determined by in situ hybridization that both NPY Y1 and Y5 receptor mRNA are expressed in the SCN of Syrian hamsters. Second, similar to our previous findings at Zeitgeber time 14 (ZT 14, where ZT 12 was the time of lights off), we found that NPY applied at ZT 18.5 onto the SCN region of brain slices maintained in vitro could block NMDA-induced phase advances of the spontaneous firing rate rhythm, and this blocking effect was probably mediated by the Y5 receptor, since co-application of Y5 receptor antagonists completely reversed the effect of NPY, while application of a Y1 receptor antagonist had no effect under the same conditions. Third, we found that co-treatment with a Y5 receptor antagonist in vivo (s.c., 10 mg/kg) not only reversed the effect of NPY applied to the SCN in vivo through a cannula but also significantly potentiated the light-induced phase advance in the absence of NPY. This is the first report of a NPY receptor antagonist having such an effect, and indicates that NPY Y5 receptor antagonists could be clinically useful for potentiating circadian system responses to light. [source] Resetting the brain clock: time course and localization of mPER1 and mPER2 protein expression in suprachiasmatic nuclei during phase shiftsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2004Lily Yan Abstract The mechanism whereby brief light pulses reset the mammalian circadian clock involves acute Per gene induction. In a previous study we investigated light-induced expression of mPer1 and mPer2 mRNA in the suprachiasmatic nuclei (SCN), with the aim of understanding the relationship between gene expression and behavioural phase shifts. In the present study, we examine the protein products of mPer1 and mPer2 genes in the core and shell region of SCN for 34 h following a phase-shifting light pulse, in order to further explore the molecular mechanism of photic entrainment. The results indicate that, during the delay zone of the phase response curve, while endogenous levels of mPER1 and mPER2 protein are falling, a light pulse produces an increase in the expression of both proteins. In contrast, during the advance zone of the phase response curve, while levels of endogenous mPER1 and mPER2 proteins are rising, a light pulse results in a further increase in mPER1 but not mPER2 protein. The regional distribution of mPER1 and mPER2 protein in the SCN follows the same pattern as their respective mRNAs, with mPER1 expression in the shell region of SCN correlated with phase advances and mPER2 in the shell region correlated with phase delays. [source] A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003V. M. King Abstract A mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen et al. (2000) PNAS, 97, 11575,11580) was used to investigate circadian function in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R, detected by a beta-galactosidase (,-GAL) tag, have a distinct distribution within the SCN, closely matching that of neurophysin (NP) neurons and extending into the region of peptide histidine isoleucine (PHI) cells. In common with NP and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2 in hVPAC2R cells confirmed their photic responsiveness. Having established their circadian properties, we tested the utility of SCN neurons expressing the hVIPR transgene as functionally and anatomically explicit markers for SCN tissue grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation into adult CD1 mice, and expressed ,-GAL, PER and PHI. Over a series of studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of 72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR transgenic grafts on a heterozygous Clock mutant background we confirmed that restored activity rhythms were conferred by the donor tissue. We conclude that the hVIPR transgene is a powerful and flexible tool for examination of circadian function in the mouse SCN. [source] The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2003David J. Cutler Abstract Expression of coherent and rhythmic circadian (, 24 h) variation of behaviour, metabolism and other physiological processes in mammals is governed by a dominant biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). Photic entrainment of the SCN circadian clock is mediated, in part, by vasoactive intestinal polypeptide (VIP) acting through the VPAC2 receptor. Here we used mice lacking the VPAC2 receptor (Vipr2,/,) to examine the contribution of this receptor to the electrophysiological actions of VIP on SCN neurons, and to the generation of SCN electrical firing rate rhythms SCN in vitro. Compared with wild-type controls, fewer SCN cells from Vipr2,/, mice responded to VIP and the VPAC2 receptor-selective agonist Ro 25-1553. By contrast, similar proportions of Vipr2,/, and wild-type SCN cells responded to gastrin-releasing peptide, arginine vasopressin or N -methyl- d -aspartate. Moreover, VIP-evoked responses from control SCN neurons were attenuated by the selective VPAC2 receptor antagonist PG 99-465. In firing rate rhythm experiments, the midday peak in activity observed in control SCN cells was lost in Vipr2,/, mice. The loss of electrical activity rhythm in Vipr2,/, mice was mimicked in control SCN slices by chronic treatment with PG 99-465. These results demonstrate that the VPAC2 receptor is necessary for the major part of the electrophysiological actions of VIP on SCN cells in vitro, and is of fundamental importance for the rhythmic and coherent expression of circadian rhythms governed by the SCN clock. These findings suggest a novel role of VPAC2 receptor signalling, and of cell-to-cell communication in general, in the maintenance of core clock function in mammals, impacting on the cellular physiology of SCN neurons. [source] Dopaminergic signalling in the rodent neonatal suprachiasmatic nucleus identifies a role for protein kinase A and mitogen-activated protein kinase in circadian entrainmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002Irina L. Schurov Abstract The circadian clock of the suprachiasmatic nuclei (SCN) of perinatal rodents is entrained by maternally derived cues. The SCN of neonatal Syrian hamsters express high-affinity D1 dopamine receptors, and the circadian activity,rest cycle of pups can be entrained by maternal injection of dopaminergic agonists. The present study sought to characterize the intracellular pathways mediating dopaminergic signalling in neonatal rodent SCN. Both dopamine and the D1 agonist SKF81297 caused a dose-dependent increase in phosphorylation of the transcriptional regulator Ca2+/cyclic AMP response element (CRE) binding protein (CREB) in suprachiasmatic GABA-immunoreactive (-IR) neurons held in primary culture. The D1 antagonist SCH23390 blocked this effect. Dopaminergic induction of pCREB-IR in GABA-IR neurons was also blocked by a protein kinase A (PKA) inhibitor, 5,24, and by the MAPK inhibitor, PD98059, whereas KN-62, an inhibitor of Ca2+/calmodulin-dependent (CAM) kinase II/IV was ineffective. Treatment with NMDA increased the level of intracellular Ca2+ in the cultured primary SCN neurons in Mg2+ -free medium, but SKF81297 did not. Blockade of CaM kinase II/IV with KN-62 inhibited glutamatergic induction of pCREB-IR in GABA-IR neurons, whereas 5,24 was ineffective, confirming the independent action of Ca2+ - and cAMP-mediated inputs on pCREB. SKF81297 caused an increase in pERK-IR in SCN cells, and this was blocked by 5,24, indicative of activation of MAPK via D1/cAMP. These results demonstrate that dopaminergic signalling in the neonatal SCN is mediated via the D1-dependent activation of PKA and MAPK, and that this is independent of the glutamatergic regulation via Ca2+ and CaM kinase II/IV responsible for entrainment to the light/dark cycle. [source] Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nucleiEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Elizabeth S. Maywood Abstract The circadian clockwork of the hypothalamic suprachiasmatic nuclei (SCN) is synchronized by light and by nonphotic cues. The core timing mechanism is cell-autonomous, based on an autoregulatory transcriptional/translational feedback loop of circadian genes and their products. This study investigated the effects of neuropeptide Y (NPY), a potent nonphotic resetting cue, and its interaction with light in regulating clock gene expression in the SCN in vivo. Injection of NPY adjacent to the SCN and transfer to darkness 7 h before scheduled lights out, shifted the circadian activity,rest cycle. Exposure to light for 1 h immediately after NPY infusion blocked this behavioural response. NPY-induced shifts were accompanied by suppression of both mPer1 and mPer2 mRNA in the SCN, assessed 3 h after infusion. mPer mRNAs were not altered 1 h after infusion. Levels of mClock mRNA or mCLOCK immunoreactivity in the SCN were not affected by NPY at either time point. In parallel to the behavioural response, the NPY-induced suppression of mPer genes in the SCN was attenuated when a light pulse was delivered immediately after the infusion. These results identify mPer1 and mPer2 as molecular targets for both photic and nonphotic (NPY-induced) resetting of the clockwork, and support a synthetic model of circadian entrainment based upon convergent up- and downregulation of mPer expression. [source] Characterization of carbonic anhydrase from Neisseria gonorrhoeaeFEBS JOURNAL, Issue 6 2001Björn Elleby We have investigated the steady state and equilibrium kinetic properties of carbonic anhydrase from Neisseria gonorrhoeae (NGCA). Qualitatively, the enzyme shows the same kinetic behaviour as the well studied human carbonic anhydrase II (HCA II). This is reflected in the similar pH dependencies of the kinetic parameters for CO2 hydration and the similar behaviour of the kinetics of 18O exchange between CO2 and water at chemical equilibrium. The pH profile of the turnover number, kcat, can be described as a titration curve with an exceptionally high maximal value of 1.7 × 106 s,1 at alkaline pH and a pKa of 7.2. At pH 9, kcat is buffer dependent in a saturable manner, suggesting a ping-pong mechanism with buffer as the second substrate. The ratio kcat/Km is dependent on two ionizations with pKa values of 6.4 and 8.2. However, an 18O-exchange assay identified only one ionizable group in the pH profile of kcat/Km with an apparent pKa of 6.5. The results of a kinetic analysis of a His66,Ala variant of the bacterial enzyme suggest that His66 in NGCA has the same function as a proton shuttle as His64 in HCA II. The kinetic defect in the mutant can partially be overcome by certain buffers, such as imidazole and 1,2-dimethylimidazole. The bacterial enzyme shows similar Ki values for the inhibitors NCO,, SCN, and N3, as HCA II, while CN, and the sulfonamide ethoxzolamide are considerably weaker inhibitors of the bacterial enzyme than of HCA II. The absorption spectra of the adducts of Co(II)-substituted NGCA with acetazolamide, NCO,, SCN,, CN, and N3, resemble the corresponding spectra obtained with human Co(II)-isozymes I and II. Measurements of guanidine hydrochloride (GdnHCl)-induced denaturation reveal a sensitivity of the CO2 hydration activity to the reducing agent tris(2-carboxyethyl)phosphine (TCEP). However, the A292/A260 ratio was not affected by the presence of TCEP, and a structural transition at 2.8,2.9 m GdnHCl was observed. [source] PER2 controls circadian periods through nuclear localization in the suprachiasmatic nucleusGENES TO CELLS, Issue 11 2007Koyomi Miyazaki Molecular circadian clock regulation engages a negative feedback loop comprising components of the negative limb, PERs and CRYs. In addition to the rhythmic transcriptional regulation of clock genes, controlled subcellular localization might contribute to the molecular mechanism of the mammalian circadian clock. To address this issue, we generated transgenic (TG) mice lines harboring either rat PER2 (rPER2) with a deleted nuclear localizing domain [NLD(,)] or intact PER2. In comparison with wild-type (WT) control, the period of the circadian locomotor rhythm in TG mice over-expressing NLD(,) PER2 was longer, while that in TG mice over-expressing intact PER2 was shorter. The nuclear entry of endogenous PER2, CRY1 and CRY2 was delayed in the suprachiasmatic nucleus (SCN) of NLD(,) PER2 TG mice under constant darkness, whereas that of mouse PER2 (mPER2) is accelerated in the SCN of intact PER2 TG mice. Under constant light, the locomotor activity of NLD(,) PER2 TG mice became arrhythmic, whereas WT animals remained rhythmic. These data indicate that PER2 controls circadian periods through nuclear localization in the SCN. In addition, sleep architecture was also affected in intact PER2 TG mice, suggesting PER2 can modulate a sleep molecular mechanism. [source] Circadian rhythm of aromatic l -amino acid decarboxylase in the rat suprachiasmatic nucleus: gene expression and decarboxylating activity in clock oscillating cellsGENES TO CELLS, Issue 5 2002Yoshiki Ishida Background: Aromatic l -amino acid decarboxylase (AADC) is the enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathways. In the brain, however, a group of AADC containing neurones is found outside the classical monoaminergic cell groups. Since such non-monoaminergic AADC is expressed abundantly in the suprachiasmatic nucleus (SCN), the mammalian circadian centre, we characterized the role of AADC in circadian oscillation. Results : AADC gene expression was observed in neurones of the dorsomedial subdivision of the SCN and its dorsal continuant in the anterior hypothalamic area. These AADC neurones could uptake exogenously applied L-DOPA and formed dopamine. AADC was co-expressed with vasopressin and the clock gene Per1 in the neurones of the SCN. Circadian gene expression of AADC was observed with a peak at subjective day and a trough at subjective night. The circadian rhythm of AADC enzyme activity in the SCN reflects the expression of the gene. Conclusions: Non-monoaminergic AADC in the SCN is expressed in clock oscillating cells, and the decarboxylating activity of master clock cells are under the control of the circadian rhythm. [source] Modifications of retinal afferent activity induce changes in astroglial plasticity in the hamster circadian clockGLIA, Issue 2 2001Monique Lavialle Abstract The circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP expression over the 24-h period. In this study, we evaluated the role of neuronal retinal input in the observed changes. Modifications of retinal input, either by rearing animals under darkness (DD) or under constant light (LL), or by suppressing afferent input (bilateral enucleation), induced drastic changes in astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP expression was evident in the area of the SCN deprived of retinal projections, whereas persistence of a rhythmic variation was in those areas still exhibiting GFAP expression. By contrast, no changes in astrocytic plasticity were detected in hamsters maintained under LL. These data suggest two fundamental roles for astrocytes within the SCN: (1) to regulate and mediate glutamate released by retinal terminals throughout the neuronal network to facilitate photic signal transmission; (2) to contribute to synchronization between suprachiasmatic neurons. GLIA 34:88,100, 2001. © 2001 Wiley-Liss, Inc. [source] Synthesis of Some Novel Thioxanthenone-Fused Azacrown Ethers, and Their Use as New Catalysts in the Efficient, Mild, and Regioselective Conversion of Epoxides to , -Hydroxy Thiocyanates with Ammonium ThiocyanateHELVETICA CHIMICA ACTA, Issue 7 2007Hashem Sharghi Abstract The regioselective ring-opening reactions of some epoxides with ammonium thiocyanate in the presence of a series of new 9H -thioxanthen-9-one-fused azacrown ethers, i.e., 7,11 (Scheme,1), and also of dibenzo[18]crown-6 (12), Kryptofix®22 (13), and benzo[15]crown-5 (14) were studied (Tables 1 and 2). The epoxides were subjected to cleavage by NH4SCN in the presence of these catalysts under mild conditions in various aprotic solvents. Reagents and conditions were identified for the synthesis of individual , -hydroxy thiocyanates in high yield and with more than 90% regioselectivity. The results can be discussed in terms of a four-step mechanism (Scheme,2): 1) formation of a complex between catalyst and NH4SCN, 2) release of SCN, from the complex, 3) reaction of the released SCN, at the sterically less hindered site of the epoxide, and 4) regeneration of the catalyst. The major advantages of this method are the high regioselectivity, the simple regeneration of the catalyst, the reuse of it through several cycles without a decrease of activity, and the ease of workup of the reaction mixtures. [source] Hydroxyl radical reactions with halogenated ethanols in aqueous solution: Kinetics and thermochemistryINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2008I. Morozov Laser flash photolysis combined with competition kinetics with SCN, as the reference substance has been used to determine the rate constants of OH radicals with three fluorinated and three chlorinated ethanols in water as a function of temperature. The following Arrhenius expressions have been obtained for the reactions of OH radicals with (1) 2-fluoroethanol, k1(T) = (5.7 ± 0.8) × 1011 exp((,2047 ± 1202)/T) M,1 s,1, (2) 2,2-difluoroethanol, k2(T) = (4.5 ± 0.5) × 109 exp((,855 ± 796)/T) M,1 s,1, (3) 2,2,2-trifluoroethanol, k3(T) = (2.0 ± 0.1) × 1011 exp((,2400 ± 790)/T) M,1 s,1, (4) 2-chloroethanol, k4(T) = (3.0 ± 0.2) × 1010 exp((,1067 ± 440)/T) M,1 s,1, (5) 2, 2-dichloroethanol, k5(T) = (2.1 ± 0.2) × 1010 exp((,1179 ± 517)/T) M,1 s,1, and (6) 2,2,2-trichloroethanol, k6(T) = (1.6 ± 0.1) × 1010 exp((,1237 ± 550)/T) M,1 s,1. All experiments were carried out at temperatures between 288 and 328 K and at pH = 5.5,6.5. This set of compounds has been chosen for a detailed study because of their possible environmental impact as alternatives to chlorofluorocarbon and hydrogen-containing chlorofluorocarbon compounds in the case of the fluorinated alcohols and due to the demonstrated toxicity when chlorinated alcohols are considered. The observed rate constants and derived activation energies of the reactions are correlated with the corresponding bond dissociation energy (BDE) and ionization potential (IP), where the BDEs and IPs of the chlorinated ethanols have been calculated using quantum mechanical calculations. The errors stated in this study are statistical errors for a confidence interval of 95%. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 174,188, 2008 [source] Inactivation of Escherichia coli and Shigella in acidic fruit and vegetable juices by peroxidase systemsJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2006I. Van Opstal Abstract Aims:, To study the bactericidal properties of the lactoperoxidase (LPER)-thiocyanate and soybean peroxidase (SBP)-thiocyanate systems at low pH, their efficiency for inactivation of Escherichia coli and Shigella in acidic fruit and vegetable juices, their effect on colour stability of the juices and interaction with ascorbic acid. Methods and Results:, Three-strain cocktails of E. coli and Shigella spp. in selected juices were supplemented with the LPER or SBP system. Within 24 h at 20°C, the LPER system inactivated both cocktails by ,5 log10 units in apple, 2,5 log10 units in orange and ,1 log10 unit in tomato juices. In the presence of SBP, browning was significant in apple juice and white grape juice, slight in pink grape juice and absent in orange or tomato juice. Ascorbic acid protected E. coli and Shigella against inactivation by the LPER system, and peroxidase systems significantly reduced the ascorbic acid content of juices. Conclusions:, Our results suggest a different specificity of LPER and SBP for SCN,, phenolic substrates of browning and ascorbic acid in acidic juices. The LPER system appeared a more appropriate candidate than the SBP system for biopreservation of juices. Significance and Impact of the Study:, This work may open perspectives towards the development of LPER or other peroxidases as biopreservatives in acidic foods. [source] Effects of SCN,/H2O2 combinations in dentifrices on plaque and gingivitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2001Michael Rosin Abstract Objectives: A 10-week, double-blind, placebo-controlled clinical study on 140 male subjects was conducted to determine the effect on plaque and gingivitis of 5 dentifrices containing various thiocyanate (SCN,)/hydrogen peroxide (H2O2) combinations. Materials and Methods: The dentifrices consisted of a gel base without any detergents or abrasives (placebo, group A) to which SCN, and/or H2O2 were added as follows: 0.1% SCN, (group B), 0.5% SCN, (group C), 0.1% SCN,/ 0.1% H2O2 (group D), 0.5% SCN,/0.1% H2O2 (group E) and 0.1% H2O2 (group F). A baseline examination was performed in which the Silness and Löe Plaque Index (PI), the Mühlemann and Son Sulcus Bleeding Index (SBI), and the amount of gingival crevicular fluid (GCF) were recorded using the Periotron 6000 on teeth 16, 12, 24, 36, 32, and 44. The subjects were randomly assigned to either the placebo group (n=40) or one of the test groups (n=20) and used their respective dentifrices over a period of 8 weeks. Finally, each group used the placebo for another 2 weeks (wash-out). Re-examinations were performed after 1, 4, and 8 weeks and the 2-week wash-out period employing the clinical parameters used at baseline. Intragroup changes were analyzed with the Wilcoxon signed-ranks test, using the baseline and wash-out points as references. The Mann-Whitney U test was used for comparisons between the treatment groups and the placebo group. Results: At the 8-week examination, the plaque index in group E (p=0.017) and group F (p=0.032) was lower than in the placebo group. The Sulcus Bleeding Index in group F after 1 week was increased (p=0.023) and the SBI in group E after 8 weeks was reduced (p=0.047) as compared to the placebo group. Conclusion: The results demonstrated that a dentifrice containing 0.5% SCN, and 0.1% H2O2 but no detergents or abrasives inhibited plaque and decreased gingivitis. Zusammenfassung Zielsetzung: Eine 10 Wochen dauernde placebokontrollierte Doppelblindstudie wurde bei 140 männlichen Probanden durchgeführt, um die Auswirkungen von 5 Zahnpasten, die verschiedene Kombinationen von Thiozyanat (SCN,) und Wasserstoffperoxide (H2O2) enthielten, auf Plaque und Gingivitis zu untersuchen. Material und Methoden: Die Zahnpasten bestanden aus einer Gelbasis ohne jegliche Detergentien oder Putzkörper (Placebo, Gruppe A), der SCN, und/oder H2O2 wie folgt beigemengt waren: 0.1% SCN, (Gruppe B), 0.5% SCN, (Gruppe C), 0.1% SCN,/0.1% H2O2 (Gruppe D), 0.5% SCN,/0.1% H2O2 (Gruppe E) und 0.1% H2O2 (Gruppe F). Zu Beginn der Studie wurden der Plaque Index (PI), der Sulkus-Blutungs-Index (SBI) und die Sulkusflüssigkeitsfließrate (SFFR) mit dem Periotron 6000 an den Zähnen 16, 12, 24, 36, 32 und 44 bestimmt. Die Probanden wurden zufällig der Placebogruppe (n=40) oder einer der 5 Testgruppen (n=20) zugewiesen und benutzten die entsprechende Zahnpasta über einen Zeitraum von 8 Wochen. Schließlich benutzte jeder Proband die Placebopasta für weitere 2 Wochen ("wash-out"). Nachuntersuchungen fanden nach 1, 4 und 8 Wochen sowie nach der "wash-out"-Periode statt. Ergebnisse: Zur 8-Wochen-Nachuntersuchung war der PI in den Gruppen E (p=0.017) und F (p=0.032) niedriger als in der Placebogruppe. Der SBI in Gruppe F war im Vergleich zur Placebogruppe nach einer Woche erhöht (p=0.023) und in Gruppe E nach 8 Wochen reduziert (p=0.047). Schlußfolgerungen: Die Ergebnisse zeigen, daß eine Zahnpasta, die 0.5% SCN, und 0.1% H2O2 aber keinerlei Detergentien oder Putzkörper enthält Plaque hemmen und Gingivitis reduzieren kann. Résumé Une étude clinique en double aveugle, controlée par un placebo, sur 10 semaines a été réalisée sur 140 sujets masculins pour déterminer les effets sur la plaque et la gingivite de 5 dentifrices contenant des combinaisons variées de thiocyanate (SCN,)/peroxyde d'hydrogene (H2O2). Les dentifrices étaient constitués d'une base de gel sans détergents ni abrasifs (placebo, groupe A) à laquelle étaient ajoutés SCN, et/ou H2O2 comme suit: 0.1% SCN, (groupe B), 0.5% SCN, (groupe C), 0.1% SCN,/0.1% H2O2 (groupe D), 0.5% SCN,/1% H2O2 (groupe E), et 0.1% H2O2 (groupe F). Un examen initial était réalise au cours duquel, l'indice de plaque de Silness et Löe (PI), l'indice de saignement sulculaire de Mühlemann et Son (SBI), et la quantité de fluide gingival (GCF) étaient enregistrés en utilisant le Periotron 6000 sur les dents 16, 12, 24, 36, 32 et 44. Les sujets étaient assignés au hasard soit dans le groupe placebo (n=20), soit dans un groupe test (n=20) et utilisaient leur dentifrices respectifs pendant une période de 8 semaines. Finalement, chaque groupe utilisait le placebo pendant 2 semaines supplémentaires (lessivage). Une réexamination était réalisée après 1, 4, 8 semaines et après la période de lessivage final de 2 semaines avec les mênes indices qu'à l'examen initial. Les modifications intragroupe étaient analysées par le test de Wilcoxon signed ranks, en utilisant les indices initiaux et ceux relevés lors de la période de lessivage. Le test de Mann-Whitney U fut utilisé pour comparer les groupes test et le groupe placebo. A l'examen de la huitième semaine, les indices de plaque du groupe E (p=0.017) et du groupe F (p=0.032) étaient plus bas que dans le groupe placebo. L'indice de saignement sulculaire du groupe F après une semaine était augmenté (p=0.023) et le SBI du groupe E après 8 semaines était diminué (p=0.047), comparé au groupe placebo. Les résultats montrent qu'un dentifrice contenant 0.5% SCN, et 0.1% H2O2, mais ni détergents, ni abrasifs, inhibe la plaque et réduit la gingivite. [source] Food-reward signalling in the suprachiasmatic clockJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Jorge Mendoza J. Neurochem. (2010) 112, 1489,1499. Abstract Under special restricted feeding conditions the mammalian circadian clock, contained in the hypothalamic suprachiasmatic nucleus (SCN), can be entrained by food. During food restriction, hungry animals are very motivated to obtain food. This motivational state could be a key component in altering the SCN timing by feeding. In order to comprehend how hedonic signals of food affect the SCN clock, we evaluated the effects of a daily palatable snack on the behavioural rhythm of mice fed ad libitum with regular food, and housed under constant darkness conditions. As light synchronization of the SCN is modulated by feeding/metabolic cues, the effects of a palatable meal coupled to a light pulse were tested on behavioural and molecular rhythms. A daily palatable snack entrained behavioural rhythms of mice in constant darkness conditions. Furthermore, palatable meal access at the activity onset reduced light-induced behavioural phase-delays and Period genes expression in the SCN. In addition, an increase in the dopamine content and Period genes expression in the forebrain of mice was observed, concomitant with a c- FOS activation in dopaminergic and orexinergic neurons, suggesting that the effects of a palatable snack on the SCN clock are mediated by the reward/arousal central systems. In conclusion, this study establishes an underlying sensitivity of the master circadian clock to changes in motivational states related to palatable food intake. [source] Circadian variations of prostaglandin E2 and F2 , release in the golden hamster retinaJOURNAL OF NEUROCHEMISTRY, Issue 4 2010Nuria De Zavalía J. Neurochem. (2009) 112, 972,979. Abstract Circadian variations of prostaglandin E2 and F2, release were examined in the golden hamster retina. Both parameters showed significant diurnal variations with maximal values at midnight. When hamsters were placed under constant darkness for 48 h, the differences in prostaglandin release between subjective mid-day and subjective midnight persisted. Western blot analysis showed that cyclooxygenase (COX)-1 levels were significantly higher at midnight than at mid-day, and at subjective midnight than at subjective mid-day, whereas no changes in COX-2 levels were observed among these time points. Immunohistochemical studies indicated the presence of COX-1 and COX-2 in the inner (but not outer) retina. Circadian variations of retinal prostaglandin release were also assessed in suprachiasmatic nuclei (SCN)-lesioned animals. Significant differences in retinal prostaglandin release between subjective mid-day and subjective midnight were observed in SCN-lesioned animals. These results indicate that hamster retinal prostaglandin release is regulated by a retinal circadian clock independent from the SCN. Thus, the present results suggest that the prostaglandin/COX-1 system could be a retinal clock output or part of the retinal clock mechanism. [source] Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in ratsJOURNAL OF NEUROCHEMISTRY, Issue 6 2009Su-xia Li Abstract Previous studies have shown that clock genes are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, other brain regions, and peripheral tissues. Various peripheral oscillators can run independently of the SCN. However, no published studies have reported changes in the expression of clock genes in the rat central nervous system and peripheral blood mononuclear cells (PBMCs) after withdrawal from chronic morphine treatment. Rats were administered with morphine twice daily at progressively increasing doses for 7 days; spontaneous withdrawal signs were recorded 14 h after the last morphine administration. Then, brain and blood samples were collected at each of eight time points (every 3 h: ZT 9; ZT 12; ZT 15; ZT 18; ZT 21; ZT 0; ZT 3; ZT 6) to examine expression of rPER1 and rPER2 and rCLOCK. Rats presented obvious morphine withdrawal signs, such as teeth chattering, shaking, exploring, ptosis, and weight loss. In morphine-treated rats, rPER1 and rPER2 expression in the SCN, basolateral amygdala, and nucleus accumbens shell showed robust circadian rhythms that were essentially identical to those in control rats. However, robust circadian rhythm in rPER1 expression in the ventral tegmental area was completely phase-reversed in morphine-treated rats. A blunting of circadian oscillations of rPER1 expression occurred in the central amygdala, hippocampus, nucleus accumbens core, and PBMCs and rPER2 expression occurred in the central amygdala, prefrontal cortex, nucleus accumbens core, and PBMCs in morphine-treated rats compared with controls. rCLOCK expression in morphine-treated rats showed no rhythmic change, identical to control rats. These findings indicate that withdrawal from chronic morphine treatment resulted in desynchronization from the SCN rhythm, with blunting of rPER1 and rPER2 expression in reward-related neurocircuits and PBMCs. [source] |