Neuroscience
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Comparative Study
Inhibitory M2 muscarinic receptors are upregulated in both axotomized and intact small diameter dorsal root ganglion cells after peripheral nerve injury.
Acetylcholine reduces nociceptive input in part by activating inhibitory M2 muscarinic receptors on primary sensory neurons, and acetylcholinesterase inhibitors and muscarinic agonists produce analgesia in humans and animals. M2 muscarinic receptors are upregulated in animals with diabetic neuropathy, but their level of expression and function after peripheral nerve injury has not been previously examined. This study tested, using intracellular Ca(2+) response to membrane depolarization, the effect of the M2 muscarinic receptor agonist bethanechol on individual dorsal root ganglion cells from normal and L5-6 spinal nerve-ligated rats, followed by M2 muscarinic receptor immunostaining. ⋯ The proportion of studied dorsal root ganglion neurons with positive M2 muscarinic receptor staining increased significantly in the injured ipsilateral L5-6 and the uninjured ipsilateral L4 ganglia, but not in the contralateral dorsal root ganglion neurons compared with normals. In contrast, the proportion of neurons responding to capsaicin significantly decreased in the injured ipsilateral L5-6 dorsal root ganglion cells. These results suggest that inhibitory M2 muscarinic receptors are upregulated in small- and medium-sized axotomized dorsal root ganglion neurons and their uninjured neighbors following nerve injury, and may represent an appropriate target for analgesia in this setting.
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We evaluated the activity of the atypical antipsychotic drug olanzapine on differentiation and gene expression in adult neural precursor cells in vitro. Neural precursors obtained from forebrain subventricular zone (SVZ)-derived neurospheres express a subset (13/24) of receptors known to bind olanzapine at high to intermediate affinities; in contrast, all 24 are expressed in the SVZ. In the presence of 10 nM, 100 nM or 1 microM olanzapine, there is no significant change in the frequency of oligodendrocytes, neurons, GABAergic neurons and astrocytes generated from neurosphere precursors. ⋯ There are no major changes in cytological differentiation in response to the drug; however, at one concentration (10 nM) there is a small but statistically significant increase in the size of glial fibrillary acidic protein-labeled astrocytes derived from neurosphere precursors. In addition, olanzapine apparently modulates expression of one serotonin receptor -- 5HT2A -- in differentiating neurosphere cultures; however, it does not modify expression of several other receptors or schizophrenia vulnerability genes. Thus, olanzapine has a limited influence on differentiation and gene expression in adult neural precursor cells in vitro.
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Comparative Study
Effect of neonatal handling on serotonin 1A sub-type receptors in the rat hippocampus.
Serotonin 1A sub-type receptors play an important role in the etiopathogenesis of depression, which is known to occur more often in females than males. Early experiences can be a predisposing factor for depression; however, the underlying cellular processes remain unknown. In an effort to address such issues, we employed neonatal handling, an experimental model of early experience, which has been previously shown to render females more vulnerable to display enhanced depression-like behavior in response to chronic stress, while it increases the ability of males to cope. ⋯ In adult animals the number of serotonin 1A sub-type receptor mRNA positive cells was increased as a result of handling in the area 1 of Ammon's horn, area 4 of Ammon's horn and dentate gyrus of males, while it was decreased only in the area 4 of Ammon's horn of females. Furthermore, the number of serotonin sub-type 1A receptor immunopositive cells, as well as [(3)H]8-hydroxy-2(di-n-propylamino)tetralin binding sites was increased in the area 1 of Ammon's horn, area 4 of Ammon's horn and dentate gyrus of handled males, whereas it was decreased in these same brain areas in the handled females. We can thus infer that neonatal handling results in alterations in postsynaptic serotonergic neurotransmission, which may contribute to the sex dimorphic effects of handling as to the vulnerability toward depression-like behavior in response to chronic stressful stimuli.
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Comparative Study
Intergeniculate leaflet: contributions to photic and non-photic responsiveness of the hamster circadian system.
The circadian visual system is able to integrate light energy over time, enabling phase response and Fos induction in the suprachiasmatic nucleus to increase in proportion to the total energy of the photic stimulus. In the present studies, the contribution of the intergeniculate leaflet to light energy integration by the hamster circadian rhythm system was evaluated. Fos protein is induced in intergeniculate leaflet neurons at much lower irradiance levels than seen in suprachiasmatic nucleus neurons. ⋯ Anatomical analysis showed that virtually no intergeniculate leaflet neurons projecting to the suprachiasmatic nucleus contain Fos induced by either light or locomotion in a novel wheel. However, cells projecting to the pretectum were found to contain novel-wheel induced Fos. The intergeniculate leaflet is implicated in the normal assessment of light by the circadian rhythm system, but the circuitry by which either photic or non-photic information gains access to the suprachiasmatic nucleus may be more complex than previously thought.
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Comparative Study
Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.
Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. ⋯ Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.