Neuroscience
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Estrogen produces a beneficial role in animal models of multiple sclerosis (MS). The effect of 17β-estradiol therapy on microglia polarization and neuroinflammation in the corpus callosum of the cuprizone-induced demyelination model has not been elucidated. In this study, mice were given 0.2% cuprizone (CPZ) for 5 weeks to induce demyelination during which they received 50 ng of 17β-estradiol (EST), injected subcutaneously in the neck region, twice weekly. ⋯ Moreover, administration of 17β-estradiol resulted in a significant reduction (∼3-fold) in transcript levels of NLRP3 inflammasome and its downstream product IL-18, compared to controls. In summary, this study demonstrated for the first time that exogenous 17β-estradiol therapy robustly leads to the reduction of M1 phenotype, stimulation of polarized M2 microglia, and repression of NLRP3 inflammasome in the corpus callosum of CPZ demyelination model of MS. The positive effects of 17β-estradiol on microglia and inflammasome seems to facilitate and accelerate the remyelination process.
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Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. ⋯ Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated. We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in T1D.
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Long-term living at high altitude causes significant impairment of cognitive function. Central neurotransmitters are potential mediators of cognitive performance. ⋯ Consistent with this result, peripheral plasma DOPA, dopamine, serotonin, 5-HIAA and glutamate were associated with brain neurotransmitter levels after chronic HH exposure in rats. These results provide experimental data indicating that neurotransmitter levels and cognitive performance are modified in chronic high-altitude exposure, with a possible causal effect.
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Cortical morphogenesis entails several neurobiological events, including proliferation and differentiation of progenitors, migration of neuroblasts, and neuronal maturation leading to functional neural circuitry. These neurodevelopmental processes are delicately regulated by many factors. Endosomal SNAREs have emerged as formidable modulators of neuronal growth, aside their well-known function in membrane/vesicular trafficking. ⋯ Notably, cortical layer 5 (L5) is distinctively disorganized in the absence of Vti1a/1b. The latter defect, coupled with an overt apoptosis of Ctip2-expressing L5 neurons, likely contributed to the substantial loss of corticospinal and callosal projections in the Vti1a/1b-deficient mouse brain. These findings suggest that Vti1a/1b serve key neurodevelopmental functions during cortical histogenesis, which when mechanistically elucidated, can lend clarity to how endosomal SNAREs regulate brain development, or how their dysfunction may have implications for neurological disorders.
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Alzheimer's disease (AD) is the most common neurodegenerative disease; thus, the search for a cure or causal therapy has become necessary. Despite intense research on this topic in recent decades, there is no curative therapy up today, and also no disease-modifying treatment has been approved. As promising approach passive immunization strategies have thereby come forth. ⋯ Further functional assays predict a protective effect of this antibody. Although, all four recombinant antibodies showed binding to amyloid-β, promising features were only detectable after conversion into a multimeric format. The multimeric scFv-Fc antibody exhibited thereby strong impact on amyloid-β clearance and inhibition of oligomerization.