Neuroscience
-
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.
-
Neuronal excitability and susceptibility to excitotoxic damage can be sex-specific, with neurons from males usually being more 'easily excitable' compared to neurons from females, especially during development. Increased excitability at an individual neuronal level can lead to the formation of hyperexcitable neuronal networks, which, consequently can make the brain more seizure prone. Both animal and clinical data suggest that males experience more frequent and severe seizures than do females. ⋯ We report a baseline sex difference in N-methyl-d-aspartate (NMDA)-induced seizure behavior and hippocampal neuronal loss, with postnatal day (PND) 14 males exhibiting more severe seizure behavior compared to females. Pretreatment with the general 5-HT receptor agonist 5-methoxytryptamine (5-MT) abolishes baseline sex differences, providing an anticonvulsant effect for males only. These sex differences appear to be at least in part organized by testosterone, as females given neonatal androgen exhibit a seizure behavior profile in between that of males and females.
-
Multi-omics Analysis of the Amygdala in a Rat Chronic Unpredictable Mild Stress Model of Depression.
Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. ⋯ Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.
-
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.