Neuroscience
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Brain-derived neurotrophic factor (BDNF) induces plasticity within the lumbar spinal circuits thereby improving locomotor recovery in spinal cord-injured animals. We examined whether lumbar spinal cord motor neurons and other ventral horn cells of spinally transected (ST) rats were stimulated to produce BDNF mRNA in response to treadmill training. Rats received complete spinal cord transections as neonates (n=20) and one month later, received four weeks of either a low (100 steps/training session; n=10) or high (1000 steps/training session; n=10) amount of robotic-assisted treadmill training. ⋯ In addition, there were significantly more motor neurons that contained BDNF mRNA labeling within processes in the ST rats that received the higher amount of treadmill training. These findings suggested that motor neurons and other ventral horn cells in ST rats synthesized BDNF in response to treadmill training. The findings support a mechanism by which postsynaptic release of BDNF from motor neurons contributed to synaptic plasticity.
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Valproate (VPA) is an anticonvulsant and mood-stabilizing drug. It is a broad-spectrum histone deacetylase inhibitor with neuroprotective effects. We investigated whether VPA reduces retinal neuronal death induced by optic nerve crush (ONC). ⋯ Furthermore, VPA upregulated levels of bcl-2, BDNF, TrkB in the retina post-injury. VPA and SB treatment resulted in the hyperacetylation of histone H3K14, attenuated histone H3K9 hypermethylation in the BDNF promoter, and promoted transcriptional activity. These results demonstrate that VPA appears to protect RGCs from ONC by inhibiting neuronal apoptosis possibly via the activation of BDNF-TrkB signaling and HDAC inhibition.
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Previous studies have shown that the amygdala plays a key role in the modulation of uncontrollable stress effect on hippocampal long-term potentiation and memory in rats. This study aimed to determine the effects of selective neurotoxic lesions of the basolateral amygdala (BLA) on stress-induced glucocorticoid receptor (GR) translocation and alteration of phosphorylated extracellular signal-regulated kinases (pERK) in the hippocampus. Intrinsic neurons of the BLA in rats were destroyed using N-methyl-d-aspartate and the rats were subjected to uncontrollable stress induced by restraint and electrical tail shocks. ⋯ In addition, the Western blot analyses showed that, in response to stress, the levels of hippocampal pERK were reduced in the sham-operated controls, but not in the rats with BLA lesions. Interestingly, the immunohistological analyses showed that BLA lesions prevented the stress-induced reductions in hippocampal pERK levels, only in the DG. These results suggested that the amygdala modulates stress-induced cognitive impairments by regulating the ERK signaling pathway in the hippocampus.
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Animals exposed to phencyclidine (PCP) during the neonatal period have fewer GABAergic interneurons in the corticolimbic area, including the hippocampus, and exhibit abnormal behaviors after attaining maturation that correspond with schizophrenic symptoms. Since a lack of inhibitory interneurons in the hippocampus has also been reported in postmortem studies of patients with schizophrenia, the deficit may induce abnormal activity of hippocampal neurons that underlies pathological states in schizophrenia. However, it remains unclear how PCP treatment during the neonatal period affects the discharge activity of hippocampal neurons in adulthood. ⋯ Further, the number of neurons with E/E-type response was higher in the PCP-treated mice than in the saline-treated mice. Finally, the attenuation of an auditory-evoked potential component, N40, to the second click (sensory gating) was blunted in the PCP-treated mice when compared with that in the saline-treated mice. These results suggest that the neonatal administration of PCP induced a deficit of inhibitory interneurons and altered discharge activity of neurons in the hippocampal CA3 region to the paired clicks, thereby inducing the deficit in sensory gating.
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Neurotrophins like brain-derived neurotrophic factor (BDNF) promote the migration of subsets of neural progenitor cells. The mechanism by which motility is increased and the functional properties of BDNF-responsive cells are not very well known. We have used the neurosphere model, combining time-lapse microscopy, immunocytochemistry, and Ca(2+) imaging, to study the effect of BDNF on parameters such as motility and neurotransmitter responsiveness of migrating neural progenitors. ⋯ Kainate-responsive cells, denoting the expression of AMPA/kainate receptors, dominated in the outer migration layers while cells responding to (S)-3,5-dihydroxyphenylglycine (DHPG) via metabotropic glutamate receptor 5 (mGluR5) dominated in the inner migration layers. BDNF did not appreciably affect the distribution of these cells but promoted the redistribution of a small subpopulation (about 20%) of N-methyl-D-aspartate (NMDA)- and GABA-responsive cells to the outermost layers of migration. The results demonstrate that BDNF does not affect cell motility per se but alters the phasic behavior of cell movement by promoting periods of high motility in a defined subpopulation of cells which give a robust Ca(2+) response to NMDA and GABA.