Neuroscience
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Alzheimer's disease (AD) is the most common cause of dementia resulting in widespread degeneration of the central nervous system with severe cognitive impairment. Despite the devastating toll of AD, the incomplete understanding of the complex molecular mechanisms hinders the expeditious development of effective cures. Emerging evidence from animal studies has shown that different brain cell types play distinct roles in the pathogenesis of AD. ⋯ Much has been discovered through genetically modified animal models, yet frequently failed translational attempts to clinical applications call for better disease models. Emerging evidence supports the significance of human-induced pluripotent stem cell (iPSC) derived brain cells in modeling disease development and progression, opening new avenues for the discovery of molecular mechanisms. This review summarizes the function of different cell types in the pathogenesis of AD, such as neurons, microglia, and astrocytes, and recognizes the potential of utilizing the rapidly growing iPSC technology in modeling AD.
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The intraparietal sulcus region, which is part of the posterior parietal cortex (PPC), has been shown to play an important role in discriminating object shapes using the fingers. Transcranial random noise stimulation (tRNS) and anodal transcranial pulsed current stimulation (tPCS) are noninvasive strategies widely used to modulate neural activity in cortical regions. Therefore, we investigated the effects of tRNS and anodal tPCS applied to left or right PPC on the tactile discrimination performance of the right index finger in 20 neurologically healthy subjects. ⋯ Conducting tRNS over the left PPC significantly reduced the GOT discrimination performance in the high-performance group. By contrast, anodal tPCS delivered to the PPC of the left and right hemispheres had no significant effect on the tactile GOT discrimination performance of the right hand. We show that transcranial electric stimulation over the PPC may improve tactile perception but the effect depends on stimulus modality, parameters, and on the stimulated hemisphere.
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The negative emotions caused by persistent pain, called affective pain, are known to seriously affect human physical and mental health. The anterior cingulate cortex (ACC), especially the rostral ACC (rACC) plays a key role in the development of this affective pain. N-methyl-d-aspartate (NMDA) receptors, which are widely distributed in the ACC, are involved in the regulation of emotional behavior. ⋯ Then, western blot was used to determine levels of phosphorylated NMDA receptor subunits GluN1, GluN2 and GluN3 as affected by the δ-opioid receptor activation. The results showed that activation of δ-opioid receptors down-regulates the phosphorylation of NMDA receptor subunits, thereby inhibiting NMDA currents, decreasing the discharge frequency of rACC pyramidal neurons, and reversing the CPA response. Thus, δ-opioid receptor activation in the rACC region can alleviate affective pain.
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Augmentation of neurogenesis and migration of newly born neurons into ectopic regions like the hilus play critical roles during the pathophysiology of acute kindled seizures. Evidence shows that disrupted in schizophrenia 1 (DISC1) has an influence on adult neurogenesis in the dentate gyrus (DG); however, its role of regulating neurogenesis and mispositioned newborn neurons in the hilus after status epilepticus (SE) remains unknown. ⋯ Unexpectedly, an interesting phenomenon was observed as well. Some glial fibrillary acidic protein (GFAP)-positive cells in the hilus appeared to encircle the DISC1-positive cells, which possibly indicated that DISC1 may participate in the process of neuronal or neural development associated with astrocytes such as phagocytosis, dendritic spine development, synaptic transmission, and developmental and synaptic plasticity.
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Although temperament has been regarded as an innate aspect of human personality, its association with proteins involved in embryonic development is unclear. Reelin, encoded by RELN, plays an important role in brain development. Herein, we investigated the association between the RELN rs7341475 (G/A) single nucleotide polymorphism, detected as a female-specific risk factor for schizophrenia, brain structure, and temperament to elucidate the role of RELN in the development of human personality. ⋯ Furthermore, of the four temperaments, the novelty seeking was significantly and positively associated with rGMV in the right superior temporal gyrus, partially overlapping with areas where differences between the rs7341475 genotypes were detected. The above findings were detected only in females, but not in males. This is the first study to demonstrate the contribution of RELN rs7341475 to differences in brain structure in Japanese females, which may indicate vulnerability to schizophrenia and variations in human personality.