Neuroscience
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As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for the treatment of brain disorders. Here, I review studies on mGluRs in the auditory system. ⋯ These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted.
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Increasing evidence points to an essential role played by neuron-derived neurosteroids, such as estrogen, on synaptic connectivity in the hippocampus. Inhibition of local estradiol synthesis results in synapse loss specifically in females, but not in males. ⋯ Cognitive deficits after inhibition of aromatase, the final enzyme of estrogen synthesis, have been seen in women, but not in men. Altogether, the data demonstrate distinct differences between genders in neurosteroid-induced synaptic stability.
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Previous neuroimaging studies of response inhibition have examined correlations between behavioral efficiency and brain activity, but the temporal stability of the correlations has largely been ignored. The present functional magnetic resonance imaging (fMRI) study demonstrates the temporal changes of the brain activity associated with performance efficiency that led to more robust brain-behavior correlations in a later part of the experimental sessions. Participants performed a stop-signal task requiring inhibition of inappropriate responses, where more efficient behavioral performance is reflected in a shorter stop-signal reaction time (SSRT). ⋯ In the cerebellar region that showed the greatest difference in correlations between the second and the first halves, the brain activity increased in efficient performers, whereas the brain activity decreased in poor performers. These results suggest the existence of multiple brain mechanisms that increase and decrease the brain activity depending on the behavioral efficiency of the performers. More practically, these results indicate that robust brain-behavior correlations can more effectively be detected in a later part of the experimental sessions.
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β-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of Aβ peptides, proposed to drive the pathological changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in four brain regions from individuals with AD and controls. ⋯ Both RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three showed similar disease stage-dependent changes with respect to NSE and GFAP. These findings indicated that the in vitro data demonstrating an effect of PPIL2 on BACE1 expression have functional relevance in vivo. Further research into BACE1-interacting proteins could provide a fruitful approach to the modulation of this protease and consequently Aβ production.
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Zellweger syndrome (ZS) is a severe peroxisomal disorder caused by mutations in peroxisome biogenesis, or PEX, genes. A central hallmark of ZS is abnormal neuronal migration and neurodegeneration, which manifests as widespread neurological dysfunction. The molecular basis of ZS neuropathology is not well understood. ⋯ We demonstrate that PEX13 brain mutants display changes that reflect an abnormal serotonergic system - decreased levels of tryptophan hydroxylase-2, the rate-limiting enzyme of serotonin (5-hydroxytryptamine, 5-HT) synthesis, dysmorphic 5-HT-positive neurons, abnormal distribution of 5-HT neurons, and dystrophic serotonergic axons. The raphe nuclei region of PEX13 brain mutants also display increased levels of apoptotic cells and reactive, inflammatory gliosis. Given the role of the serotonergic system in brain development and motor control, dysfunction of this system would account in part for the observed neurological changes of PEX13 brain mutants.