Neuroscience
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Rats repeatedly exposed to variable prenatal stress (PNS) exhibit schizophrenia-like behavioral signs such as social withdrawal, elevations in amphetamine-induced locomotor activity, deficits in sensory-motor gating, as well as impairments in memory-related task performance. However, to date there have been no studies designed to test the hypothesis that variable PNS would lead to disruptions in sustained attention and inhibitory response control (i.e., symptoms also commonly observed in schizophrenia and other neuropsychiatric disorders such as attention-deficit hyperactivity disorder). In the current study, the effects of variable PNS in rats were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a 5-choice serial reaction time task (5C-SRTT). ⋯ In contrast, atomoxetine decreased premature and timeout responses in both PNS and control subjects in the VITI version of the task and improved accuracy in the PNS subjects. The results suggest that exposure to variable PNS in rats results in impairments of sustained attention and inhibitory response control and that these deficits can be exacerbated by NMDA antagonism and improved by a norepinephrine uptake inhibitor. Collectively, these data further support the premise that variable PNS in rats is a valid model system for the study of neuropsychiatric disorders and their treatment.
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It is well known that Gamma-aminobutyric acid (GABA) plays an important role in signal transduction in the central nervous system. However, the function of GABA in the peripheral nervous system, including sensory ganglions, is still unclear. In this study we have characterized the expression, cellular distribution, and function of GABA(B) receptor subunits, and the recently discovered GABA(B) auxiliary subunits, K(+) channel tetramerization domain-containing (KCTD) proteins, in rat trigeminal ganglion (TG) neuronal cells, which are devoid of synapses. ⋯ This correlated with observed differences in voltage-dependent K(+) current responses to baclofen in voltage-clamped TG neuronal cells. The functional diversity of the GABA(B)ergic regulation on the excitability of the TG neuronal cell bodies could be due to the heterogenous expression of KCTD proteins, and subsequent regulation of plasma membrane K(+) channels. Taken together with our previous demonstration of a local GABA(A) receptor-mediated system in rat TG, we provide an updated GABAergic model in the rat TG that incorporates both GABA(A)- and GABA(B)-receptor systems.
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Cholinergic neurotransmission in the hippocampus is involved in cognitive functions, including learning and memory. Strategies to enhance septohippocampal cholinergic neurotransmission may therefore be of therapeutic value to limit cognitive decline during cholinergic dysfunction. In addition to current strategies being developed, such as the use of acetylcholinesterase inhibitors, enhancing acetylcholine (ACh) release may be critical for optimal cholinergic neurotransmission. ⋯ VAChT overexpression enhanced the release of ACh from ex vivo hippocampal slices. From these findings, we conclude that VAChT overexpression is sufficient to enhance ACh release in the hippocampal formation. It remains to be established whether, in cases of cholinergic deficits, increasing VAChT expression would re-establish adequate levels of cholinergic neurotransmission, thereby providing a valid therapeutic target.
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The expression of Arc and Homer 1a (H1a) depends on neural activity. This study was designed to determine hippocampal Arc and H1a mRNA expression levels after spatial learning with differing behavioral task demands. Forty-four male rats were distributed into 11 groups of four. ⋯ The level of mRNA expression at different stages of maze learning was determined using real-time reverse-transcription polymerase chain reaction (qRT-PCR). Significantly elevated expression of both Arc and H1a was observed. The orchestrated expression levels of both genes were correlated with the behavioral task demand level and behavioral performance.
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Evidence from clinical and experimental studies indicates that degeneration of nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). The present study was designed to investigate the neuroprotective potential of theaflavin (TF) on oxidative stress, monoamine transporters and behavioral abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration. ⋯ Pre-treatment with TF reduces oxidative stress, improves motor behavior and expression of DAT and VMAT2 in striatum and substantia nigra. These results indicate that TF might be beneficial in mitigating MPTP-induced damage of dopaminergic neurons, possibly via its neuroprotective and its antioxidant potential.