Neuroscience
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Chronic subcortical hyperdopaminergic activity is associated with the positive symptoms of schizophrenia and is a hallmark feature of a number of animal models of the disorder. However, the molecular changes induced by increased dopaminergic activity associated with schizophrenia are not clear. Increased levels of ΔFosB have been found in association with chronic subcortical hyperdopaminergic activity following repeated cocaine or amphetamine administration. ⋯ DARPP32 Thr(75) is selectively phosphorylated by cdk-5 and phosphorylation of DARPP32 at Thr(75) suppresses DARPP32 activity, a critical step in the regulation of both glutamatergic and dopaminergic activity in neurons. We also found that apomorphine-induced locomotor activity was further increased following intra-accumbens infusions of roscovitine, a cdk-5 blocker, in a dose-dependent manner. Our results indicate that chronic hyperdopaminergic activity, as seen in schizophrenia, may affect glutamate and dopamine function in the NA via ΔFosB-mediated transcriptional modulation.
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This study aimed to better characterize the sensorimotor mechanisms underlying motor resonance, namely the relationship between motion perception and movement production in patients suffering from Alzheimer's disease (AD). This work first gives a kinematic description of AD patients' upper limb movements, then it presents a simple paradigm in which a dot with different velocities is moved in front of the participant who is instructed to point to its final position when it stopped. AD patients' actions, as well as healthy elderly participants, were similarly influenced by the dot velocity, suggesting that motor resonance mechanisms are not prevented by pathology. ⋯ In particular, the preservation of the motor resonance mechanisms, not dependent on conscious awareness, constitutes an intact basis upon which clinicians could model both physical and cognitive interventions for healthy elderly and AD patients. Furthermore, the evaluation of the inhibitory functions, less sensitive to the level of education than other methods, might be useful for screening test combined with the traditional AD techniques. However, further investigations to understand if this feature is specific to AD or is present also in other neurodegenerative diseases are needed.
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Previous studies have shown that a 2-week treatment with 40 mg/kg corticosterone (CORT) in rats suppresses hippocampal neurogenesis and decreases hippocampal brain-derived neurotrophic factor (BDNF) levels and impairs spatial learning, all of which could be counteracted by voluntary wheel running. BDNF and insulin-like growth factor (IGF-1) have been suggested to mediate physical exercise-enhanced hippocampal neurogenesis and cognition. Here we examined whether such running-elicited benefits were accompanied by corresponding changes of peripheral BDNF and IGF-1 levels in a rat model of stress. ⋯ Running counteracted cognitive deficit and restored hippocampal cell proliferation following chronic CORT treatment; but without corresponding changes in plasma BDNF and IGF-1 levels. The results suggest that the beneficial effects of acute stress on cognitive improvement may be mediated by BDNF-enhanced synaptic plasticity that is hippocampal cell proliferation-independent, whereas chronic stress may impair cognition by decreasing hippocampal cell proliferation and BDNF levels. Furthermore, the results indicate a trend in changes of plasma BDNF levels associated with a significant alteration in hippocampal levels, suggesting that treatment with running/CORT for 4 weeks may induce a change in central levels of hippocampal BDNF level, which may not lead to a significant change in peripheral levels.
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We have demonstrated previously that nicotine affords neuroprotective and anti-inflammatory effects against intracerebral hemorrhage (ICH)-associated neuropathological changes. The present study was undertaken to clarify whether subtype-specific agonists of nicotinic acetylcholine receptors (nAChRs) could preserve tissue integrity in mouse ICH model in vivo. ICH was induced by unilateral injection of collagenase into the striatum of male C57BL/6 mice. ⋯ PNU-282987 decreased the number of activated microglia/macrophages accumulating in the perihematoma region at 3 days after ICH, in a dose-dependent manner. On the other hand, the number of microglia/macrophages in the central region of hematoma at early phase of pathology (6 h after ICH) was increased by 10mg/kg PNU-282987. These results suggest that α7 nAChR agonist can provide neuroprotective effect on ICH-induced injury, independently of its anti-inflammatory actions.
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Circadian rhythms affect olfaction by an unknown molecular mechanism. Independent of the suprachiasmatic nuclei, the mammalian olfactory bulb (OB) has recently been identified as a circadian oscillator. The electrical activity in the OB was reported to be synchronized to a daily rhythm and the clock gene, Period1, was oscillatory in its expression pattern. ⋯ We observed significant changes in the messenger RNA and protein expression of our targets across 24 or 48 h. Whereas most targets were rhythmic by some measures, only GluR1 mRNA and protein were both rhythmic by the majority of our tests of rhythmicity across all time scales. Differential expression of these synaptic proteins over the light/dark cycle may underlie circadian synchronization of action potential firing in the OB or modify synaptic interactions that would be predicted to impact olfactory coding, such as alteration of granule cell inhibition, increased number of available AMPARs to bind glutamate, or an increased gap junction conductance between mitral/tufted cells.