Neuroscience
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Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is thought to have environmental (toxin) and genetic contributions. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) induces pathological features of PD including loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatal dopamine (DA) depletion. We previously described the striatal transcriptional response following acute MPTP administration in MPTP-sensitive C57BL/6J mice. ⋯ However neither paraquat nor MPTP elicits cross-attenuation. Thus exposure to specific toxins triggers distinct transcriptional responses in striatum that are influenced by prior exposure to the same toxin. The prolonged refractory period described here for MPTP could explain at the molecular level the reported discrepancies between different MPTP administration regimens and may have implications for our understanding of the relationship between environmental toxin exposure and PD.
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The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2' cassettes can alter the pharmacology and regulation of this receptor. ⋯ NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, AMY, and the HIPP. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward-seeking behaviors.
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A number of studies have demonstrated that the relative timing of audiovisual stimuli is especially important for multisensory integration of speech signals although the neuronal mechanisms underlying this complex behavior are unknown. Temporal coincidence and congruency are thought to underlie the successful merging of two intermodal stimuli into a coherent perceptual representation. It has been previously shown that single neurons in the non-human primate prefrontal cortex integrate face and vocalization information. ⋯ When tested with a dynamic face-vocalization stimulus that had been temporally offset (asynchronous) one-third of multisensory cells in VLPFC demonstrated a change in response compared to the response to the natural, synchronous face-vocalization movie. Our results indicate that prefrontal neurons are sensitive to the temporal properties of audiovisual stimuli. A disruption in the temporal synchrony of an audiovisual signal which results in a change in the firing of communication related prefrontal neurons could underlie the loss in intelligibility which occurs with asynchronous speech stimuli.
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Caspases are implicated in neuronal death in neurodegenerative and other central nervous system (CNS) diseases. In a rat model of human immunodeficiency virus type 1 (HIV-1) associated neurocognitive disorders (HAND), we previously characterized HIV-1 envelope gp120-induced neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In this model, neuronal apoptosis occurred probably via gp120-induced reactive oxygen species (ROS). ⋯ Prior gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) into the CP before injecting gp120 there reduced levels of gp120-induced caspases, recapitulating the effect of antioxidant enzymes on gp120-induced apoptosis observed by TUNEL. Thus, HIV-1 gp120 increased caspases expression in the CP. Prior antioxidant enzyme treatment mitigated production of these caspases, probably by reducing ROS levels.
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Despite an extremely rich and complex auditory environment, human beings categorize sounds effortlessly. While it is now well-known that this ability is a result of complex interaction of bottom-up processing of low-level acoustic features and top-down influences like evolutionary relevance, it is yet unclear how these processes drive categorization. The objective of the current study was to use functional neuroimaging to investigate the contribution of these two processes for category selectivity in the cortex. ⋯ Category selectivity was not observed for any other category of sounds. Our findings suggest a potential role of evolutionary relevance for cortical processing of sounds. While this seems to be an appealing proposition, further studies are required to explore the role of top-down mechanisms arising from such features to drive category selectivity in the brain.