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Monoaminergic Neurons (monoaminergic + neuron)
Selected AbstractsZinc finger gene fez - like functions in the formation of subplate neurons and thalamocortical axonsDEVELOPMENTAL DYNAMICS, Issue 3 2004Tustomu Hirata Abstract fez - like (fezl) is a forebrain-expressed zinc finger gene required for the formation of the hypothalamic dopaminergic and serotonergic (monoaminergic) neurons in zebrafish. To reveal its function in mammals, we analyzed the expression of the mouse orthologue of fezl and generated fezl -deficient mice by homologous recombination. Mouse fezl was expressed specifically in the forebrain from embryonic day 8.5. At mid-gestation, fezl expression was detected in subdomains of the forebrain, including the dorsal telencephalon and ventral diencephalon. Unlike the zebrafish fezl mutant too few, the fezl -deficient mice displayed normal development of hypothalamic monoaminergic neurons, but showed abnormal "hyperactive" behavior. In fezl,/, mice, the thalamocortical axons (TCA) were reduced in number and aberrantly projected to the cortex. These mutants had a reduced number of subplate neurons, which are involved in guiding the TCA from the dorsal thalamus, although the subplate neurons were born normally. These results suggest that fezl is required for differentiation or survival of the subplate neurons, and reduction of the subplate neurons in fezl -deficient mice leads to abnormal development of the TCA, providing a possible link between the transcriptional regulation of forebrain development and hyperactive behavior. Developmental Dynamics 230:546,556, 2004. © 2004 Wiley-Liss, Inc. [source] Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Catarina Å. Owesson Abstract Monoamine oxidase-A knockout (MAO-A KO) mice have elevated brain serotonin (5-HT) and noradrenaline (NA) levels, and one would therefore anticipate increased monoamine release and compensatory changes in other aspects of presynaptic monoamine function. In this study we used voltammetry in brain slices from the locus coeruleus (LC), dorsal raphe (DRN) and striatum (CPu) in 7-week-old MAO-A KO and C3H control mice to measure stimulated monoamine efflux and its control by amine transporters and autoreceptors. In LC, peak NA efflux on stimulation (99 pulses, 100 Hz) was higher in MAO-A KO than C3H mice (938 ± 58 nm cf. 511 ± 42 nm; P < 0.001). The NA uptake half time (t½) was longer in MAO-A KO than in C3H mice (6.0 ± 0.9 s cf. 1.9 ± 0.3 s; P < 0.001) and the selective NA reuptake inhibitor desipramine (50 nm) had a smaller effect in MAO-A KO mice. NA transporter binding was significantly lower in the LC of MAO-A KO mice compared to C3H controls (P < 0.01) but not in the DRN. The ,2 agonist dexmedetomidine (10 nm) decreased stimulated NA efflux more in C3H than in MAO-A KO mice (73.3% cf. 29.6% inhibition, P < 0.001). In DRN, peak 5-HT efflux on stimulation (99 pulses, 100 Hz) was greater (P < 0.01) in MAO-A KO (262 ± 44 nm) than C3H mice (157 ± 16 nm). Moreover, 5-HT uptake t½ was longer (P < 0.05) in MAO-A KO than in C3H mice (8.8 ± 1.1 s cf. 4.9 ± 0.6 s, P < 0.05) and the effect of citalopram (75 nm) was attenuated in MAO-A KOs. Serotonin transporter binding was also lower in both the DRN and LC of MAO-A KO mice. The 5-HT1A agonist 8-OH-DPAT (1 µm) decreased 5-HT efflux more in C3H than in MAO-A KO mice (38.3% inhibition cf. 21.6%, P < 0.001). In contrast, there were no significant differences between MAO-A KO and C3H mice in CPu dopamine efflux and uptake and the effect of the D2/3 agonist quinpirole was similar in the two strains. In summary, MAO-A KO mice show major dysregulation of monoaminergic presynaptic mechanisms such as autoreceptor control and transporter kinetics. [source] Three-photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2008S.K. Kaushalya Abstract Recent experiments on monoaminergic neurons have shown that neurotransmission can originate from somatic release. However, little is known about the quantity of monoamine available to be released through this extrasynaptic pathway or about the intracellular dynamics that mediate such release. Using three-photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the somata of primary cultured neurons contain a large number of serotonin-filled vesicles arranged in a perinuclear fashion. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe. We estimate that the soma of a cultured neuron on an average contains about 9 fmoles of serotonin in about 450 vesicles (or vesicle clusters) of ,370 nm average diameter. A substantial fraction (>30%) of this serotonin is released with a time scale of several minutes by K+ -induced depolarization or by para-chloroamphetamine treatment. The amount of releasable serotonin stored in the somatic vesicles is comparable to the total serotonin content of all the synaptic vesicles in a raphe neuron, indicating that somatic release can potentially play a major role in serotonergic neurotransmission in the mammalian brain. © 2008 Wiley-Liss, Inc. [source] Neurofibrillary tangles and deposition of oxidative products in the brain in cases of myotonic dystrophyNEUROPATHOLOGY, Issue 2 2006Reiko Oyamada Myotonic dystrophy (MyD) is a neuromuscular degenerative disorder that is neuropathologically characterized by minor changes, such as the presence of neurofibrillary tangles (NFT), thalamic inclusions and functional brainstem lesions. In the current study, we conducted an immunohistochemical analysis to examine the distribution of NFT and formation of oxidative products in the brain specimens of 12 patients with MyD. Neurofibrillary tangles were found in the limbic system and/or the brainstem of all the cases examined but there were no senile plaques. The density of distribution of the NFT was not significantly correlated with clinicopathological findings, although cases with fewer NFT in the brain frequently showed sleep disturbances and lack of spontaneity. Nuclear and cytoplasmic immunoreactivities for 8-hydroxy-2,-deoxyguanosine and advanced glycation end products were observed in the glial cells and/or neurons in the brainstem, but not in the cerebral cortex. On the other hand, 10 out of the 12 cases showed cytoplasmic immunoreactivity for 4-hydroxy-2-nonenal-modified protein (4-HNE) in neurons of the temporal cortex and raphe nucleus. Deposition of 4-HNE was also recognized in the hippocampus and mesencephalic central gray matter, but not in the subiculum. The distribution pattern of the immunoreactivity for 4-HNE showed no clear correlation with either the psychological disturbances or the distribution of the NFT. Altered expression of monoaminergic neurons in the brainstem of MyD patients has already been reported, and it is worth noting that most of our cases showed NFT in the brainstem. The selective deposition of 4-HNE in the limbic system and brainstem suggests that lipid peroxidation may be involved in the neurodegenerative process in MyD. Using immunohistochemical analysis to determine the distribution of neurotransmitters in the mesencephalic central gray matter and/or pontine raphe nucleus may help elucidate the relationship between the clinical abnormalities, distribuion of NFT, and 4-HNE deposition in the brain in patients with MyD. [source] The neurochemistry of waking and sleeping mental activity: The disinhibition-dopamine hypothesisPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2002CLAUDE GOTTESMANN Abstract This paper describes a hypothesis related to the neurochemical background of sleep-waking mental activity which, although associated with subcortical structures, is principally generated in the cerebral cortex. Acetylcholine, which mainly activates cortical neurons, is released at the maximal rate during waking and rapid eye movement (REM) sleep dreaming stage. Its importance in mental functioning is well-known. However, brainstem-generated monoamines, which mainly inhibit cortical neurons, are released during waking. Both kinds of influences contribute to the organized mentation of waking. During slow wave sleep, these two types of influence decrease in intensity but maintain a sufficiently high level to allow mental activity involving fairly abstract pseudo-thoughts, a mode of activity modelled on the diurnal pattern of which it is a poor reply. During REM sleep, the monoaminergic neurons become silent except for the dopaminergic ones. This results in a large disinhibition and the maintained dopamine influence may be involved in the familiar psychotic-like mental activity of dreaming. Indeed, in this original activation,disinhibition state, the increase of dopamine influence at the prefrontal cortex level could explain the almost total absence of negative symptoms of schizophrenia during dreaming, while an increase in the nucleus accumbens is possibly responsible for hallucinations and delusions, which are regular features of mentation during this sleep stage. [source] | |||||||||||||