Neuroscience
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Comparative Study
Microglial cell death induced by a low concentration of polyamines.
Pathological activation of microglia, which reside quiescently in physiological CNS, contributes various neurodegenerative diseases. Endogenous polyamines, spermidine (SPD) and spermine (SPM) are known to be activators of cell proliferation and differentiation. We examined the effect of polyamines on microglial activation in culture. ⋯ Fragmented DNA in the cytosol increased dose dependently with SPM; EC(50) was less than 10 microM. Furthermore, most of the cells after 24 h incubation with 10 microM SPD and SPM were positive for terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling. These results suggest that microglial cell death is induced by a low concentration of polyamines via an apoptotic process rather than necrotic one.
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Comparative Study
Increased c-Fos expression in the centromedial nucleus of the thalamus in metabotropic glutamate 8 receptor knockout mice following the elevated plus maze test.
Ligands for metabotropic glutamate 8 (mGlu8) receptors, such as (S)-2-amino-4-phosphonobutanoic acid and (S)-3,4-dicarboxyphenylglycine suppress CNS excitability via presynaptic regulation of glutamate release and are anticonvulsant in mice. These observations suggest that mGlu8 receptors play a role in the regulation of neuronal excitability. To further characterize the role of mGlu8 receptors in vivo, the mGlu8 receptor knockout mouse was generated. ⋯ Basal c-Fos expression in the absence of EPM exposure did not differ between wild-type and mGlu8 receptor knockout mice in any brain region we examined. As the centromedial nucleus of the thalamus is important in regulating sensory information to higher brain regions, these results support the hypothesis that mGlu8 receptors are involved in the response to certain novel, aversive environments. In particular, the deletion of the mGlu8 receptor reduced the threshold of neuronal activation in stress-related brain regions such as the centromedial nucleus of the thalamus.
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Comparative Study
Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin.
The peptide hormone ghrelin is known to be present within stomach and, to a lesser extent, elsewhere in gut. Although reports suggest that gastric function may be modulated by ghrelin acting via the vagus nerve, the gastrointestinal distribution and functions of its receptor, the growth hormone secretagogue receptor (GHS-R), are not clear and may show signs of species-dependency. This study sought to determine the cellular localisation and distribution of GHS-R-immunoreactivity (-Ir) using immunofluorescent histochemistry and explore the function of ghrelin in both human and rat isolated gastric and/or colonic circular muscle preparations in which nerve-mediated responses were evoked by electrical field stimulation. ⋯ When examined under similar conditions, in both rat distal colon (n=4-6, P>0.05 each) and human ascending (n=3) and sigmoid (n=1) colon, these concentrations of ghrelin were without effect (P>0.05 each). The data suggest that ghrelin has the potential to profoundly affect gastrointestinal functions in both species and at least one of these functions is to exert a gastric prokinetic activity. Moreover, we suggest that this activity of ghrelin is mediated via the enteric nervous system, in addition to known vagus nerve-dependent mechanisms.
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Comparative Study
Detection and discrimination of carvone enantiomers in rats with olfactory bulb lesions.
Rats with lesions of dorsal and dorsolateral bulbar sites known to be differentially responsive to carvone enantiomers were tested for their ability to detect (+)-carvone, to discriminate between (+)-carvone from (-)-carvone, and to discriminate (+)-carvone from mixtures of both enantiomers after they had been pre-trained or not pre-trained on these tasks prior to surgery. In postoperative tests, rats pre-trained on the enantiomer discrimination problems made somewhat fewer errors than those not pre-trained, but experimental rats performed as well as controls (those that had one intact olfactory bulb) within both conditions and on each task. These results indicate that removal of most bulbar sites known to be differentially responsive to carvone enantiomers and the consequent disruption of normal patterns of bulbar input produced in response to carvones are largely without effect on the ability of rats to discriminate between these odors.
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To investigate the role of neurotransmitter secretion in the development and stabilization of synapses, the innervation of the diaphragm and intercostal muscles was studied in munc18-1 null mutant mice, which lack regulated secretion. We found that this mutant is completely devoid of both spontaneous and evoked neuromuscular transmission throughout embryonic development. At embryonic day (E) 14, axonal targeting and main branching of the phrenic nerve were normal in this mutant, but tertiary branches were elongated and no terminal branches were observed at this stage, in contrast to control littermates. ⋯ In contrast, sensory ganglia in the dorsal root showed no obvious degeneration. These data suggest that regulated secretion is not essential for initial axon path finding, clustering of acetylcholine receptors, acetylcholinesterase or the formation of synapses. However, in the absence of regulated secretion, the maintenance of the motor neuronal system, organization of nerve terminal branches and stabilization of synapses is impaired and a-neural postsynaptic elements persist.