Neuroscience
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The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. ⋯ No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress.
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Gonadectomy in adult male rats significantly impairs spatial working memory, behavioral flexibility and other functions associated with the prefrontal cortex (PFC). However, the mechanisms through which this occurs are largely unknown. In this study, intracortical drug challenge with the selective N-methyl-d-aspartate receptor (NMDAR) antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) was combined with Barnes maze testing, gonadectomy (GDX) and hormone replacement (17β-estradiol, testosterone propionate) to explore the contributions of NMDAR-mediated activity within the PFC to hormone effects on spatial cognition in adult male rats. ⋯ Together these findings suggest that hormone regulation of NMDAR-mediated activity specifically within the PFC may be fundamental to the effects of gonadal steroids on spatial cognition in males. Our findings further identify NMDAR antagonists as potentially novel, non-steroidal means of attenuating the cognitive deficits that can accompany gonadal hormone decline in human males in aging, clinical cases of hypogonadalism and in certain neurologic and psychiatric illnesses. Accordingly, it may be important to obtain in males the kind of detailed knowledge concerning hormone effects on, for example, the channel and electrophysiological properties of NMDAR that currently exists for the female brain.
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The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. ⋯ In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.
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In a previous study, we demonstrated that inflammation suppressed inward rectifying K(+) (Kir) currents in satellite glial cells (SGCs) from the trigeminal ganglia (TRGs) and that this impairment of glial potassium homeostasis in the trigeminal ganglion (TRG) contributed to trigeminal pain. The aim of the present study was to investigate whether activation of GABAB receptors modulates the Kir current in SGCs using in vivo patch-clamp and immunohistochemical techniques. Immunohistochemically, we found that immunoreactivity for glial-specific Kir channel subunit Kir4.1 and the GABAB receptor was co-expressed in SGCs from the TRGs. ⋯ Baclofen-induced potentiation of the Kir current was abolished by co-application of 3-amino-2-(4-chlorophenyl)-2-hydroxyprophylsulfonic acid (saclofen). In addition, baclofen significantly potentiated the density of the Ba(2+)-sensitive Kir current, and resulted in hyperpolarization of the mean membrane potential. These results suggest that activation of GABAB receptors potentiates the Kir current in SGCs and that GABA released from the TRG neuronal soma could contribute to buffering of extracellular K(+) concentrations following excitation of TRG neurons during the processing of sensory information, including the transmission of noxious stimuli.
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Apart from therapeutic discovery, the study of mild traumatic brain injury (mTBI) has been focused on two challenges: why do a majority of individuals recover with little concern, while a considerable proportion suffer with persistent and often debilitating symptomology; and, how do mild injuries significantly increase risk for an early-onset neurodegeneration? Owing to a lack of observable damage following mTBI, this study was designed to determine if there were changes in neuronal morphology, synaptic connectivity, and epigenetic patterning that could contribute to the manifestation of persistent neurological dysfunction. Prefrontal cortex tissue from male and female rats was used for Golgi-Cox analysis along with the profiling of changes in gene expression (BDNF, DNMT1, FGF2, IGF1, Nogo-A, OXYR, and TERT) and telomere length (TL), following a single mTBI or sham injury in the juvenile period. ⋯ The results from the neuroanatomical measures and changes in gene expression indicate that the mTBI disrupts normal pruning processes that are typically underway at this point in development. In addition, there are significant interactions between the social environment and epigenetic processes that work in concert to perpetuate neurological dysfunction.