Home About us Contact
|
Home About us Contact | ||
|
|
||
Neuronal Populations (neuronal + population)
Kinds of Neuronal Populations Selected AbstractsThe Differential Susceptibility of Specific Neuronal Populations: Insights from Huntington's DiseaseIUBMB LIFE, Issue 6 2003Ian Mitchell Abstract Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene. IUBMB Life, 55: 293-298, 2003 [source] Distributions of estrogen receptors alpha and beta in sympathetic neurons of female rats: Enriched expression by uterine innervationDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2002Elena V. Zoubina Abstract Estrogen modulates many features of the sympathetic nervous system, including cell numbers and ganglion synapses, and can induce uterine sympathetic nerve degeneration. However, distributions of estrogen receptors , and , within sympathetic neurons have not been described, and their regulation by target tissue or estrogen levels has not been explored. We used immunofluorescence and retrograde tracing to define estrogen receptor expression in sympathetic neurons at large in pre- and paravertebral ganglia and in those projecting to the uterine horns. Estrogen receptor , immunoreactivity was present in 29 ± 1%, while estrogen receptor , was expressed by 92 ± 1% of sympathetic neurons at large. The proportions of neurons expressing these receptors were comparable in the superior cervical and thoraco-lumbar paravertebral ganglia from T11 through L5, and in the suprarenal, celiac, and superior mesenteric prevertebral ganglia. Injections of FluoroGold into the uterine horns resulted in labeled neurons, with peak occurrences in T13, L1, and the suprarenal ganglion. Uterine-projecting neurons showed small but significantly greater incidence of estrogen receptor , expression relative to the neuronal population at large, whereas the proportion of uterine-projecting neurons with estrogen receptor ,-immunoreactivity was nearly threefold greater. Numbers of estrogen receptor-expressing neurons were not altered by acute estrogen administration. We conclude that the vast majority of sympathetic neurons express estrogen receptor , immunoreactive protein, whereas a smaller, presumably overlapping subset expresses the estrogen receptor ,. Expression of the latter apparently can be enhanced by target-mediated mechanisms. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 14,23, 2002 [source] Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of , and , receptor activation on proliferation and neurite elongationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Kurt F. Hauser Abstract Although opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin-derived peptides, as well as specific , and ,, but negligible ,, opioid receptors. The developmental effects of opioids were highly selective. Morphine-induced , receptor activation inhibited DNA synthesis, while a preferential ,2 -receptor agonist ([d -Ala2]-deltorphin II) or Met-enkephalin, but not the ,1 agonist [d -Pen2, d -Pen5]-enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous , and , opioid ligand,receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors. [source] The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN) and neuropeptide studyJOURNAL OF ANATOMY, Issue 2 2006E. P. K. Mensah-Brown Abstract In this study we examined the superior colliculus of the midbrain of the one-humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti-neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal population as well as for the enkephalins, somatostatin (SOM) and substance P (SP). It was found that, unlike in most mammals, the superior colliculus is much larger than the inferior colliculus. The superior colliculus is concerned with visual reflexes and the co-ordination of head, neck and eye movements, which are certainly of importance to this animal with large eyes, head and neck, and apparently good vision. The basic neuronal architecture and lamination of the superior colliculus are similar to that in other mammals. However, we describe for the first time an unusually large content of neurons in the superior colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid. We classified the majority of these neurons as small (perimeters of 40,50 µm), and localized diffusely throughout the superficial grey and stratum opticum. In addition, large pyramidal-like neurons with perimeters of 100 µm and above were present in the intermediate grey layer. Large unipolar cells were located immediately dorsal to the deep grey layer. By contrast, small neurons (perimeters of 40,50 µm) immunopositive to SOM and SP were located exclusively in the superficial grey layer. We propose that this system may be associated with a pain-inhibiting pathway that has been described from the periaqueductal grey matter, juxtaposing the deep layers of the superior colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be important in relation to the camel's life in the harsh environment of its native deserts, often living in very high temperatures with no shade and a diet consisting largely of thorny branches. [source] Cerebellar granule cells cultured from adolescent rats express functional NMDA receptors: an in vitro model for studying the developing cerebellumJOURNAL OF NEUROCHEMISTRY, Issue 2 2008R. Lisa Popp Abstract In the developing rat cerebellum functional NMDA receptors (NMDARs) expressing the NR2C subunit have been identified on or after postnatal day 19. We obtained primary cultured cells from 19- to 35-day-old rat cerebellum that expressed few oligodendrocytes or astrocytes. Cultured cells were immunoreactive for neuron-specific proteins thus indicating a neuronal population. The primary neuron present was the granule cell as indicated by immunofluorescence for the GABAA alpha 6 subunit. Whole-cell patch-clamp experiments indicated that functional NMDARs were present. Functional characteristics of NMDARs expressed in cerebellar granule cells (CGCs) obtained from adolescent animals were similar to those previously reported for NMDARs expressed in CGCs obtained from neonatal rats. Cultured CGCs obtained from older animals contained NMDARs that were inhibited by EtOH and were less sensitive to the NR2B subunit-specific antagonist Ro 25-6981. Furthermore, NMDA-induced currents were smaller than those observed in CGCs. Western blot analysis indicated the presence of the NMDA NR2A and NR2C subunits, but not the NR2B in cultures obtained from the adolescent rats. CGCs obtained from adolescent rats express functional NMDARs consistent with a developmental profile observed in vivo. [source] Dopaminergic neurons intrinsic to the striatumJOURNAL OF NEUROCHEMISTRY, Issue 6 2007Philippe Huot Abstract The striatum , the largest integrative component of the basal ganglia , harbors a population of neurons that express the enzyme tyrosine hydroxylase (TH), a faithful marker of dopaminergic neurons. The dopaminergic nature of these neurons is further supported by the fact that they express the dopamine (DA) transporter (DAT) and the nuclear orphan receptor Nurr1, a transcription factor essential for the expression of the DA phenotype by midbrain neurons. The vast majority of these neurons are morphologically similar to the medium-sized aspiny striatal interneurons and they all express the enzyme GAD65. The striatal TH-positive neurons increase markedly in number in animal models of Parkinson's disease (PD), where striatal DA concentrations are low, but this increase is abolished by L-dopa treatment. Hence, local DA concentrations appear to regulate the numerical density of this ectopic neuronal population, a phenomenon that is more likely the result of a shift in the phenotype of preexistent striatal interneurons rather than the recruitment of newborn neurons that will develop a DA phenotype. Altogether, these findings suggest that striatal TH-positive neurons act as a local source of DA and, as such, are part of a compensatory mechanism that could be artificially enhanced to alleviate or delay PD symptoms. [source] Laminar variation in neuronal viability and trophic dependence in neocortical slicesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2001Mary M. Niblock Abstract Organotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental access with significant preservation of cellular context and relationships. Within a slice, however, a variety of factors may cause individual classes of neurons to respond differently to the culture environment. Differences in deafferentation, cellular maturation, trophic dependence and ongoing naturally occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental results significantly. In this study, we examined the distribution and prevalence of cell death among neurons in each cortical layer in organotypic slices. In addition, we assessed the ability of several neurotrophic factors to ameliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal death in culture, which could not be accounted for by the pattern of programmed cell death in vivo. In addition, neurons in the six layers of the neocortex differed in the degree to which they could be rescued by neurotrophic factors. These data suggest that differential neuronal death and rescue are important considerations in studies utilizing organotypic slices and may represent particularly confounding variables in studies of effects of trophic factors in such preparations. J. Neurosci. Res. 65:455,462, 2001. © 2001 Wiley-Liss, Inc. [source] Transcriptional regulation of mesencephalic dopaminergic neurons: The full circle of life and deathMOVEMENT DISORDERS, Issue 3 2008Kambiz N. Alavian PhD Abstract Since mesencephalic dopaminergic neurons are associated to one of the most prominent human neurodegenerative ailments, Parkinson's disease, the molecular mechanism underlying their development and adult cellular properties has been the subject of intense investigations. Throughout life, transcription factors determine the fate of this neuronal population and control essential processes such as localization in the ventral midbrain, their neurotransmitter phenotype, their target innervations and synapse formation. Studies of transcription factors, such as Nurr1, Pitx3, Engrailed-1/2, and Lmx1a/b, have not only revealed importance of these genes during development, but also roles in the long-term survival and maintenance of these neurons. In this review, we will discuss the function of these transcription factors throughout the life of mesencephalic dopaminergic neurons and their value in the study of the disease mechanism. © 2007 Movement Disorder Society [source] Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brainDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007David Rotllant Abstract Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Calcium imaging of epileptiform events with single-cell resolutionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Tudor Badea Abstract Epileptic discharges propagate through apparently normal circuits, although it is still unclear how this recruitment takes place. To understand the role of different classes of neurons in neocortical epilepsy, we have developed a novel imaging assay that detects which neurons participate in epileptiform discharges. Using calcium imaging of neuronal populations during bicuculline-induced spontaneous epileptiform events in slices from juvenile mouse somatosensory cortex, we find that fast calcium transients correlate with epileptiform field potentials and intracellular depolarizing shifts and can be used as an optical signature that a given neuron has participated in an epileptiform event. Our results demonstrate a novel method to characterize epileptiform events with single-cell resolution. In addition, our data are consistent with an important role for layer 5 in generating neocortical seizures and indicate that subgroups of neurons are particularly prone to epileptiform recruitment. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 215,227, 2001 [source] Conditional ablation of neurones in transgenic miceDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Anthony R. Isles Abstract Conditional targeted ablation of specific cell populations in living transgenic animals is a very powerful strategy to determine cell functions in vivo. This approach would be of particular value to study the functions of distinct neuronal populations; however, the transgene of choice for conditional cell ablation studies in mice, the herpes simplex virus thymidine kinase gene, cannot be used to ablate neurones as its principal mode of action relies on cell proliferation. Here we report that expression of the E.coli nitroreductase gene (Ntr) and metabolism of the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) to its cytotoxic derivative can be used to conditionally and acutely ablate specific neuronal populations in vivo. As proof of principal, we have ablated olfactory and vomeronasal receptor neurones by expressing Ntr under the control of the olfactory marker protein (OMP) gene promoter. We demonstrate that following CB1954 administration, olfactory and vomeronasal receptor neurones expressing the transgene were selectively eliminated from the olfactory epithelium (OE), and projections to the olfactory bulb (OB) were lost. The functional efficacy of cell ablation was demonstrated using a highly sensitive behavioural test to show that ablated mice had lost the olfactory ability to discriminate distinct odors and were consequently rendered anosmic. Targeted expression of Ntr to specific neuronal populations using conventional transgenes, as described here, or by "knock-in" gene targeting using embryonic stem cells may be of significant value to address the functions of distinct neuronal populations in vivo. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 183,193, 2001 [source] Brain distribution of myosin Va in rainbow trout Oncorhynchus mykissACTA ZOOLOGICA, Issue 1 2008Kátia Gisele Oliveira Rancura Abstract This study presents data on myosin Va localization in the central nervous system of rainbow trout. We demonstrate, via immunoblots and immunocytochemistry, the expression of myosin Va in several neuronal populations of forebrain, midbrain, hindbrain and spinal cord. The neuronal populations that express myosin Va in trout constitute a very diverse group that do not seem to have many specific similarities such as neurotransmitters used, cellular size or length of their processes. The intensity of the immunoreactivity and the number of immunoreactive cells differ from region to region. Although there is a broad distribution of myosin Va, it is not present in all neuronal populations. This result is in agreement with a previous report, which indicated that myosin Va is approximately as abundant as conventional myosin II and kinesin, and it is broadly involved in neuronal motility events such as axoplasmatic transport. Furthermore, this distribution pattern is in accordance with what was shown in rats and mice; it indicates phylogenetic maintenance of the myosin Va main functions. [source] Effects of hyperventilation on fast goal-directed limb movements in spinocerebellar ataxia type 6EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2001M.-U. Manto It has been shown previously that hyperventilation modifies the features of the nystagmus in cerebellar patients (Walker and Zee, 1999). It has been hypothesized that hyperventilation influences the oculomotor control through a metabolic effect on cerebellar calcium channels, which play a critical role in the firing behaviour of neuronal populations in the cerebellum. This hypothesis has been tested here by analysing fast goal-directed limb movements before and after hyperventilation in spinocerebellar ataxia type 6 (SCA-6), a disease associated with a polyglutamine expansion in the , 1-A voltage-dependent calcium channel. Cerebellar hypermetria associated with fast distal single-joint movements was found to be increased following hyperventilation in patients presenting SCA-6 but remained unchanged in patients with idiopathic late-onset cerebellar degeneration (ILOCA). This is a new provocative test to enhance distal dysmetria in SCA-6. The present results strengthen the hypothesis of Walker and Zee. It is suggested that hyperventilation enhances the defective calcium transfers in SCA-6, resulting in an impairment of the calcium influx in particular into Purkinje cells involved in the control of fast goal-directed voluntary movements. [source] The patterns of spontaneous Ca2+ signals generated by ventral spinal neurons in vitro show time-dependent refinementEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Sara Sibilla Abstract Embryonic spinal neurons maintained in organotypic slice culture are known to mimic certain maturation-dependent signalling changes. With such a model we investigated, in embryonic mouse spinal segments, the age-dependent spatio-temporal control of intracellular Ca2+ signalling generated by neuronal populations in ventral circuits and its relation with electrical activity. We used Ca2+ imaging to monitor areas located within the ventral spinal horn at 1 and 2 weeks of in vitro growth. Primitive patterns of spontaneous neuronal Ca2+ transients (detected at 1 week) were typically synchronous. Remarkably, such transients originated from widespread propagating waves that became organized into large-scale rhythmic bursts. These activities were associated with the generation of synaptically mediated inward currents under whole-cell patch-clamp. Such patterns disappeared during longer culture of spinal segments: at 2 weeks in culture, only a subset of ventral neurons displayed spontaneous, asynchronous and repetitive Ca2+ oscillations dissociated from background synaptic activity. We observed that the emergence of oscillations was a restricted phenomenon arising together with the transformation of ventral network electrophysiological bursting into asynchronous synaptic discharges. This change was accompanied by the appearance of discrete calbindin immunoreactivity against an unchanged background of calretinin-positive cells. It is attractive to assume that periodic oscillations of Ca2+ confer a summative ability to these cells to shape the plasticity of local circuits through different changes (phasic or tonic) in intracellular Ca2+. [source] Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Camila L. Zold Abstract There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves (,direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. ,Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism. [source] Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75NTREUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Rafal Butowt Abstract The common receptor for neurotrophins, p75, has important roles in internalization and trafficking of neurotrophins along axons. Recent studies show that an astonishing array of proteins, including lectins, pathogens and neurotoxins, bind the p75 receptor, suggesting that they can hijack and utilize this receptor for trafficking between neuronal populations within the nervous system. Such pathogens include the neurologically important rabies viruses, prion proteins, ,-amyloid and possibly tetanus toxin. These proteins may hijack existing transport machineries designed to traffick neurotrophins, thus allowing the infiltration and distribution of pathogens and toxins among vulnerable neuronal populations with devastating effects, as seen in rabies, prion encephalopathies, Alzheimer's disease and tetanic muscle spasm. The discovery of an entry and transport machinery that is potentially shared between pathogens and neurotrophins sheds light ono trafficking systems in the nervous system and may assist the design of novel therapeutic avenues that prevent or slow the progression of diverse chronic and acute neurological disorders. [source] Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapsesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002A. Parducz Abstract The ovarian hormone estradiol induces morphological changes in the number of synaptic inputs in specific neuronal populations. However, the functional significance of these changes is still unclear. In this study, the effect of estradiol on the number of anatomically identified synaptic inputs has been assessed in the hypothalamic arcuate nucleus. The number of axo-somatic, axodendritic and spine synapses was evaluted using unbiased stereological methods and a parallel electrophysiological study was performed to assess whether synaptic anatomical remodelling has a functional consequence on the activity of the affected neurons. Estradiol administration to ovariectomized rats induced a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses and an enhancement of the frequency of neuronal firing. These results indicate that oestrogen modifications in firing frequency in arcuate neurons are temporally linked to anatomical modifications in the numerical balance of inhibitory and excitatory synaptic inputs. [source] Innervation of interneurons immunoreactive for VIP by intrinsically bursting pyramidal cells and fast-spiking interneurons in infragranular layers of juvenile rat neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Jochen F. Staiger Abstract Cortical columns contain specific neuronal populations with characteristic sets of connections. This wiring forms the structural basis of dynamic information processing. However, at the single-cell level little is known about specific connectivity patterns. We performed experiments in infragranular layers (V and VI) of rat somatosensory cortex, to clarify further the input patterns of inhibitory interneurons immunoreactive (ir) for vasoactive intestinal polypeptide (VIP). Neurons in acute slices were electrophysiologically characterized using whole-cell recordings and filled with biocytin. This allowed us to determine their firing pattern as regular-spiking, intrinsically bursting and fast-spiking, respectively. Biocytin was revealed histochemically and VIP immunohistochemically. Sections were examined for contacts between the axons of the filled neurons and the VIP-ir targets. Twenty pyramidal cells and five nonpyramidal (inter)neurons were recovered and sufficiently stained for further analysis. Regular-spiking pyramidal cells displayed no axonal boutons in contact with VIP-ir targets. In contrast, intrinsically bursting layer V pyramidal cells showed four putative single contacts with a proximal dendrite of VIP neurons. Fast-spiking interneurons formed contacts with two to six VIP neurons, preferentially at their somata. Single as well as multiple contacts on individual target cells were found. Electron microscopic examinations showed that light-microscopically determined contacts represent sites of synaptic interactions. Our results suggest that, within infragranular local cortical circuits, (i) fast-spiking interneurons are more likely to influence VIP cells than are pyramidal cells and (ii) pyramidal cell input probably needs to be highly convergent to fire VIP target cells. [source] Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndromeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Jean-Charles Bensadoun Abstract Ciliary neurotrophic factor prevents behavioural deficits and striatal degeneration in rat and primate models of Huntington's disease. Interleukin-6, another member of the cytokine family, and the chimeric molecule (IL6/IL6R) in which interleukin-6 and its soluble receptor are fused, have been shown to exert trophic action on various neuronal populations in the central nervous system. Therefore, we investigated the neuroprotective effect of these two molecules in the quinolinic acid model of Huntington's disease. LacZ-, interleukin-6- and IL6/IL6R-expressing lentiviral vectors were stereotaxically injected into the striatum of Wistar rats. Three weeks later the animals were lesioned through the intrastriatal injection of 180 nmol of quinolinic acid. The extent of the striatal damage was significantly diminished in the rats that had been treated with interleukin-6 or IL6/IL6R. The neuroprotective effect was, however, more pronounced with the IL6/IL6R chimera than with interleukin-6 as indicated by the volume of the lesions (38.6 ± 10% in the IL6/IL6R group, 63.3 ± 3.6% in the IL-6 group and 84.3 ± 2.9% in the control group). Quantitative analysis of striatal interneurons further demonstrated that the IL6/IL6R chimera is more neuroprotective than IL-6 on ChAT- and NADPH-d-immunoreactive neurons. These results suggest that the IL6/IL6R chimera is a potential treatment for Huntington's disease. [source] Synaptically released 5-HT modulates the activity of tonically discharging neuronal populations in the rostral ventral medulla (RVM)EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000Pascale Piguet Abstract There is substantial evidence for an important modulating role of monoamines (catecholamines and serotonin, 5-HT) in the rostral ventral medulla (RVM), a region which plays an important role in cardiovascular and nociceptive functions. We investigated in slices the role of endogenous monoamines in the synaptic control of the activity of rat RVM neuronal populations using intracellular recordings in the lateral RVM plus lateral aspect of nucleus paragigantocellularis lateralis. A triple-labelling protocol allowed us to identify the location of impaled neurons and their eventual monoaminergic phenotype within the serotonergic and catecholaminergic populations of the RVM. Focal electrical stimulation revealed the existence of a functional monoaminergic input onto RVM neurons which was mediated by endogenous 5-HT acting at inhibitory 5-HT1A receptors but did not involve noradrenergic neurotransmission. The slow 5-HT-mediated inhibitory postsynaptic potential (IPSP) was only observed in the regularly discharging neurons, which were found to be neither catecholaminergic nor serotonergic. The synaptic release of 5-HT was, itself, under an inhibitory control involving GABAA (,-aminobutyric acid) receptors. Moreover, we characterized the effect of the 5-HT-releasing agent fenfluramine on this functional 5-HT-mediated synaptic transmission. Our results show that the effect of fenfluramine is biphasic consisting of an initial prolongation of the serotonergic IPSP followed by a decrease in amplitude. Our data provide a basis for the previously reported inhibitory effects of exogenously applied serotonin agonists/antagonists on the autonomic functions controlled by the RVM. This 5-HT pathway, which functionally links the serotonergic and catecholaminergic regions, might play an important role in cardiovascular and nociceptive functions. [source] Generation of a transgenic mouse line expressing GFP-Cre protein from a Hoxb4 neural enhancerGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2008Elena Rivkin Abstract Here, we describe a transgenic mouse line, in which expression of green fluorescent protein fused to Cre recombinase (GFP-Cre) is directed by the early neuronal enhancer (ENE) of Hoxb4. In E9.0,13.5 transgenic embryos, Cre activity coincided with endogenous Hoxb4 throughout the neural tube up to the r6/r7 boundary in the hindbrain, the dorsal root ganglia, and the Xth cranial ganglia. Unexpectedly, Cre activity was also consistently detected in the trigeminal (Vth) cranial nerve, which is devoid of endogenous Hoxb4 expression. Strong GFP dependent fluorescence appeared slightly later in E9.5,E11.5 embryos, and reflected the later expression pattern expected for Hoxb4-ENE directed expression in the neural tube up to the r7/r8 not r6/r7 boundary. Thus, with the exception of the trigeminal nerve, this reporter faithfully reproduces endogenous embryonic neural Hoxb4 expression, and provides an excellent reagent for in vivo gene manipulations in neuronal Hoxb4 positive cells as well as the developing trigeminal nerve. This transgenic mouse line should prove especially useful for determining the fate map of neuronal populations arising in rhombomeres 7 and 8 on its own and in combination with the small set of other existing rhombomere-specific Cre recombinase expressing lines. genesis 46:119,124, 2008. © 2008 Wiley-Liss, Inc. [source] Task-related gamma-band dynamics from an intracerebral perspective: Review and implications for surface EEG and MEGHUMAN BRAIN MAPPING, Issue 6 2009Karim Jerbi Abstract Although non-invasive techniques provide functional activation maps at ever-growing spatio-temporal precision, invasive recordings offer a unique opportunity for direct investigations of the fine-scale properties of neural mechanisms in focal neuronal populations. In this review we provide an overview of the field of intracranial Electroencephalography (iEEG) and discuss its strengths and limitations and its relationship to non-invasive brain mapping techniques. We discuss the characteristics of invasive data acquired from implanted epilepsy patients using stereotactic-electroencephalography (SEEG) and electrocorticography (ECoG) and the use of spectral analysis to reveal task-related modulations in multiple frequency components. Increasing evidence suggests that gamma-band activity (>40 Hz) might be a particularly efficient index for functional mapping. Moreover, the detection of high gamma activity may play a crucial role in bridging the gap between electrophysiology and functional imaging studies as well as in linking animal and human data. The present review also describes recent advances in real-time invasive detection of oscillatory modulations (including gamma activity) in humans. Furthermore, the implications of intracerebral findings on future non-invasive studies are discussed. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Movement gating of beta/gamma oscillations involved in the N30 somatosensory evoked potentialHUMAN BRAIN MAPPING, Issue 5 2009Ana Maria Cebolla Abstract Evoked potential modulation allows the study of dynamic brain processing. The mechanism of movement gating of the frontal N30 component of somatosensory evoked potentials (SEP) produced by the stimulation of the median nerve at wrist remains to be elucidated. At rest, a power enhancement and a significant phase-locking of the electroencephalographic (EEG) oscillation in the beta/gamma range (25,35 Hz) are related to the emergence of the N30. The latter was also perfectly identified in presence of pure phase-locking situation. Here, we investigated the contribution of these rhythmic activities to the specific gating of the N30 component during movement. We demonstrated that concomitant execution of finger movement of the stimulated hand impinges such temporal concentration of the ongoing beta/gamma EEG oscillations and abolishes the N30 component throughout their large topographical extent on the scalp. This also proves that the phase-locking phenomenon is one of the main actors for the N30 generation. These findings could be explained by the involvement of neuronal populations of the sensorimotor cortex and other related areas, which are unable to respond to the phasic sensory activation and to phase-lock their firing discharges to the external sensory input during the movement. This new insight into the contribution of phase-locked oscillation in the emergence of the N30 and in its gating behavior calls for a reappraisal of fundamental and clinical interpretation of the frontal N30 component. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [source] Neurocalcin-like immunoreactivity in embryonic stages of the gastropod molluscs Aplysia californica and Lymnaea stagnalisINVERTEBRATE BIOLOGY, Issue 3 2001Amanda J.G. Dickinson Neurocalcin is a calcium-binding protein that has been localized in neural and non-neural tissues of vertebrates, the arthropod Drosophila melanogaster, and in juveniles and adults of the mollusc Aplysia californica. We examine the distribution of neurocalcin in pre-hatching stages of the molluscs A. californica and Lymnaea stagnalis to elucidate where this calcium-binding protein functions in early development, as well as to localize novel neuronal populations in early stages of ontogeny. Aplysia neurocalcin (ApNc)-like immunoreactivity was localized in shell-secreting cells in embryonic stages of both A. californica and L. stagnalis. In A. californica, central and anterior regions of the embryo were diffusely labeled, as were a few identifiable neurons in veliger stages, On the other hand, in L. stagnalis, ApNc-like immunoreactivity was clearly detected in cells and fibers in the same locations as neuronal elements that have been previously identified very early in development and throughout the embryonic period using techniques to localize specific transmitters and peptides. Furthermore, additional neurons are also identified with anti- ApNc in this species. Establishing the distribution of neurocalcin-like proteins in embryonic stages of these two molluscs provides the first step to understanding the role of such proteins during development. [source] Anatomic distribution of apoptosis in medulla oblongata of infants and adultsJOURNAL OF ANATOMY, Issue 2 2008A. Porzionato Abstract The aim of the study was to evaluate the distribution of apoptosis in the medullary nuclei of infants and adults who died of hypoxic-ischaemic injury. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) in brainstems from 22 adults (7 subjects who died of opiate intoxication, 15 who died of other hypoxic-ischaemic injury) and 10 infants. The nuclei examined included the hypoglossal, dorsal motor nucleus of the vagus, nucleus tractus solitarii, nucleus of the spinal trigeminal tract, cuneate, vestibular and inferior olivary nuclei. A morphometric analysis with the optical disector method was performed to calculate the mean percentages (± standard deviation) of TUNEL-positive neuronal and glial cells for the sample populations. Opiate deaths did not have higher apoptotic indices than other adult hypoxic-ischaemic deaths. Statistically significant differences between adults and infants were found in the neuronal apoptotic indices of the cuneate (28.2 ± 16.3% vs. 6.9 ± 8.7%), vestibular (24.7 ± 15.0% vs. 11.3 ± 11.4%), nucleus tractus solitarii (11.2 ± 11.2% vs. 2.3 ± 2.4%), dorsal motor nucleus of the vagus (6.8 ± 8.5% vs. 0.1 ± 0.2%) and hypoglossal (6.6 ± 5.7% vs. 0.1 ± 0.2%), indicating higher resistance of the neuronal populations of these infant medullary nuclei to terminal hypoxic-ischaemic injury or post-mortem changes. Differences in neuronal apoptotic index were also statistically significant among nuclei, suggesting differential characteristics of survival. Nuclei with higher neuronal apoptotic indices were the cuneate, vestibular and nucleus of the spinal trigeminal tract, which are located in the lateral medullary tegmentum and share the same vascular supply from the posterior inferior cerebellar artery. [source] Cell death mechanisms in neurodegenerationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2001K. A. Jellinger Abstract Progressive cell loss in specific neuronal populations often associated with typical cytoskeletal protein aggregations is a pathological hallmark of neurodegenerative disorders, but the nature, time course and molecular causes of cell death and their relation to cytoskeletal pathologies are still unresolved. Apoptosis or alternative pathways of cell death have been discussed in Alzheimer's disease and other neurodegenerative disorders. Apoptotic DNA fragmentation in human brain as a sign of neuronal injury is found too frequent as to account for continous neuron loss in these slowly progressive processes. Morphological studies revealed extremely rare apoptotic neuronal death in Alzheimer's disease but yielded mixed results for Parkinson's disease and other neurodegenerative disorders. Based on recent data in human brain, as well as in animal and cell culture models, a picture is beginning to emerge suggesting that, in addition to apoptosis, other forms of programmed cell death may participate in neurodegeneration. Better understanding of the molecular players will further elucidate the mechanisms of cell death in these disorders and their relations to cytoskeletal abnormalities. Susceptible cell populations in a proapoptotic environment show increased vulnerability towards multiple noxious factors discussed in the pathogenesis of neurodegeneration. In conclusion, although many in vivo and in vitro data are in favor of apoptosis involvement in neurodegenerative processes, there is considerable evidence that very complex events may contribute to neuronal death with possible repair mechanisms, the elucidation of which may prove useful for future prevention and therapy of neurodegenerative disorders. [source] NAALADase (GCP II) inhibitors protect in models of amyotrophic lateral sclerosis (ALS)JOURNAL OF NEUROCHEMISTRY, Issue 2002A. G. Thomas Chronic glutamate toxicity is implicated in the pathogenesis of ALS. The neuropeptide N-acetyl-aspartyl glutamate (NAAG) appears to function both as a storage form for glutamate and as a neuromodulator at glutamatergic synapses. Catabolism of NAAG by N-acetylated-,-linked acidic dipeptidase (NAALADase; also termed glutamate carboxypeptidase II), yields N-acetyl aspartate (NAA) and glutamate. Since prior studies demonstrate an up-regulation of NAALADase in motor cortex and increased levels of NAA and glutamate in the CSF of ALS patients, we hypothesized that inhibition of NAALADase could protect against neuronal degeneration in ALS. Neuroprotective effects of two NAALADase inhibitors were assessed. 2-(Phosphonomethyl)pentanedioic acid (2-PMPA) decreased motor neuron loss and prevented loss of choline acetyltransferase (ChAT) activity in an in vitro model of ALS wherein chronic glutamate toxicity was induced by blocking glutamate transport. Gross morphology was preserved in 2-PMPA-treated cultures. In a SOD-1 transgenic mouse model of ALS, oral administration of a structurally different NAALADase inhibitor (GPI 5693) increased survival by 29 days and delayed onset of clinical symptoms by 17 days. Preliminary analysis of spinal cord pathology revealed severe neuronal depletion and astrocytosis with white matter changes in control mice. In mice treated with GPI 5693, normal neuronal populations with modest vacuolar changes were observed. These data suggest that NAALADase inhibition may provide an exciting therapeutic approach to the devastating disease, ALS. [source] Stroke Injury in Rats Causes an Increase in Activin A Gene Expression Which is Unaffected by Oestradiol TreatmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2006M. Böttner Abstract Activins are members of the transforming growth factor-, superfamily that exert neurotrophic and neuroprotective effects on various neuronal populations. To determine the possible function of activin in stroke injury, we assessed which components of the activin signalling pathway were modulated in response to middle cerebral artery occlusion (MCAO). Furthermore, because oestradiol replacement protects against MCAO-induced cell death, we explored whether oestradiol replacement influences activin gene expression. Female Sprague-Dawley rats underwent permanent MCAO and the expression of activins and their corresponding receptors was determined by semiquantitative reverse transcriptase-polymerase chain reaction at 24 h after onset of ischaemia. We observed up-regulation of activin ,A and activin type I receptor A mRNA in response to injury. Dual-label immunocytochemistry followed by confocal z-stack analysis showed that the activin A expressing cells comprised neurones. Next, we monitored the time course of activin ,A mRNA expression in oestradiol- or vehicle-treated rats at 4, 8, 16 and 24 h after MCAO via in situ hybridisation. Starting at 4 h after injury, activin ,A mRNA was up-regulated in cortical and striatal areas in the ipsilateral hemisphere. Activin ,A mRNA levels in the cortex increased dramatically with time and were highest at 24 h after the insult, and oestradiol replacement did not influence this increase. [source] Sensitivity of Galanin- and Melanin-Concentrating Hormone-Containing Neurones to Nutritional Status: An Immunohistochemical Study in the Ovariectomized EweJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2003E. Chaillou Abstract The sensitivities of galanin and melanin-concentrating hormone (MCH) neuronal systems to nutrition are poorly understood in sheep compared to rodents. The aim of this study was to describe the changes in the numbers of galanin and MCH neurones in ovariectomized ewes submitted to different nutritional levels. In the first experiment, ewes were fed ad libitum or food deprived for 24 h. In the second experiment, two groups of ewes were fed at maintenance level (group 100) or undernourished (group 40) for 167 days, after which one-half of each group was killed or refed ad libitum (group 100R and 40R) for 4 days. The MCH neuronal population located in the lateral hypothalamic area was not affected by these nutritional changes. Long-term undernutrition enhanced the number of galanin neurones located in the infundibular nucleus and the dorsal hypothalamic area (DHA), refeeding resulted in an increase of neurones in the DHA and preoptic area, but short-term starvation had no effect on any galanin subpopulations. Our data suggest that the sensitivity of MCH neuronal populations to nutrition in sheep differs from that of rodents. Various populations of galanin-containing neurones differ in sensitivity in ewes subjected to long undernutrition and refeeding but not to short starvation. [source] Effects of Chronic Oestrogen Replacement on Stress-Induced Activation of Hypothalamic-Pituitary-Adrenal Axis Control PathwaysJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. V. Dayas Abstract Oestrogen replacement therapy reportedly suppresses hypothalamic-pituitary-adrenal (HPA) axis responses to an emotional stressor in postmenopausal women. However, most studies in the rat suggest a facilitatory role for oestrogen in the control of HPA axis function. One explanation for this difference may be the regimen of oestrogen replacement: during oestrogen replacement therapy, oestrogen levels are low and constant whereas most animal studies examined the HPA axis response when oestrogen levels are rising. In the present study, we assessed HPA axis stress responses in mature ovariectomized rats after plasma oestrogen levels had been maintained at physiological levels for a prolonged period (25 or 100 pg/ml for 7 days). In the case of both an emotional stressor (noise) and a physical stressor (immune challenge by systemic interleukin-1, administration), oestrogen replacement suppressed stress-related Fos-like immunolabelling, in hypothalamic neuroendocrine cells and plasma adrenocorticotropin hormone responses. From the present data, and past reports, it appears unlikely that these effects of oestrogen are due to a direct action on corticotropin-releasing factor or oxytocin cells. Therefore, to obtain some indication of oestrogen's possible site(s) of action, Fos-like immunolabelling was mapped in the amygdala and in brainstem catecholamine groups, which are neuronal populations demonstrating substantial evidence of involvement in the generation of HPA axis stress responses. In the amygdala, oestrogen replacement suppressed central nucleus responses to immune challenge, but not to noise. Amongst catecholamine cells, oestrogen replacement was more effective against responses to noise than immune challenge, suppressing A1 and A2 (noradrenergic) and C2 (adrenergic) responses to noise, but only A1 responses to immune challenge. These data suggest that, as in postmenopausal women on oestrogen replacement therapy, chronic low-level oestrogen replacement can suppress HPA axis stress responses in the rat. Moreover, oestrogen appears to exert effects at multiple sites within putative HPA axis control pathways, even though most of the relevant neuronal populations do not contain genomic receptors for this gonadal steroid and the pattern of oestrogen action differs for an emotional vs a physical stressor. [source] | |||||||||||||||||||||||||||||||