Neuroscience
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Review
Relationship of APOE with Alzheimer's Disease and Other Neurological Disorders: An Updated Review.
Alzheimer's disease (AD) and other neurodegenerative diseases, for which there is no effective cure, cause great social burden. Apolipoprotein E (APOE) is an important lipid transporter, which has been shown to have a close relationship with AD and other neurological disorders in an increasing number of studies, suggesting its potential as a therapeutic target. In this review, we summarize the recent advances in clinical and basic research on the role of APOE in the pathogenesis of multiple neurological diseases, with an emphasis on the new associations between APOE and AD, and between APOE and depression. The progress of APOE research in Parkinson's disease (PD) and some other neurological diseases is briefly discussed.
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In previous psychophysical work we found that luminance contrast is integrated over retinal area subject to contrast gain control. If different mechanisms perform this operation for a range of superimposed retinal regions of different sizes, this could provide the basis for size-coding. To test this idea we included two novel features in a standard adaptation paradigm to discount more pedestrian accounts of repulsive size-aftereffects. ⋯ For a given stimulus patch, this delivers a blurred step-function of responses across the population, with contrast and size encoded by the height and lateral position of the step. Unlike for textbook population coding schemes, our human results (N = 4 male, N = 4 female) displayed two asymmetries: (i) size aftereffects were greatest for targets smaller than the adaptor, and (ii) on that side of the function, results did not return to baseline, even when targets were 25% of adaptor diameter. Our results and emergent model properties provide evidence for a novel dimension of visual coding (size) and a novel strategy for that coding, consistent with previous results on contrast detection and discrimination for various stimulus sizes.
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Mild traumatic brain injuries (mild TBIs) can affect both males and females, but females are more likely to report long-term psychological complications, including changes in mood and generalized anxiety. Additionally, reproductive cycle phase has been shown to affect mild TBI symptom expression within females. These variances may result from sex differences in mild TBI-induced alterations to neurotransmission in brain regions that influence mood and emotion, possibly mediated by sex steroids. ⋯ In contrast, mild TBI had little effect on SERT expression. However, SERT expression differed between sexes and varied with the cycle phase. These findings demonstrate that regulation of neurotransmission following mild TBI differs between males and females, with implications for behavioral outcomes and the efficacy of therapeutic strategies.
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Cullin 3 (CUL3), a member of Cullin-RING ubiquitin ligase family, regulates multiple intracellular pathways. CUL3 expression in peripheral immune cells is highly associated with the development of stroke, while little is known about the mechanism of how CUL3 participates in cerebral ischemia/reperfusion (I/R) injury. In this study, we showed that CUL3 was obviously upregulated in brain tissues of male rats received middle cerebral artery occlusion (MCAO) and reperfusion and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neurons. ⋯ These findings suggested that CUL3-mediated cerebral I/R injury might be not achieved through WNK3 signaling but other pathways. Furthermore, CUL3 inhibition suppressed ubiquitin-mediated degradation of Nrf2 and activated Nrf2 signaling by increasing the nuclear translocation of Nrf2 and expression levels of HO-1 and NQO-1. Taken together, CUL3 exacerbates cerebral I/R injury potentially due to its negative regulation of Nrf2 activation.
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Cellular morphology and synaptic configuration are key determinants of neuronal function and are often modified under pathological conditions. In the first nucleus of the central auditory system, the cochlear nucleus (CN), principal bushy neurons specialize in processing temporal information of sound critical for hearing. These neurons alter their physiological properties during aging that contribute to age-related hearing loss (ARHL). ⋯ While somatic AN synapses degenerated substantially with age, as quantified by VGluT1-labeled puncta volume, no significant difference was observed in the total volume of dendritic synapses between young and old mice. Consequently, synaptic density on dendrites was significantly higher in old mice. The findings suggest that dendritic degeneration and altered synaptic innervation in bushy neurons during aging may underlie their changed physiological activity and contribute to the development of ARHL.