Neuroscience
-
Previous studies have shown that α-synuclein (α-Syn) aggregates derived from the brains of patients with Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit different phosphorylation, cytotoxicity, and seeding activity. However, the mechanism underlying the differences remains poorly understood. Here, recombinant human α-Syn was incubated in the plasma of patients with PD and MSA, and the oligomers formed in the plasma (PD-O-α-Syn and MSA-O-α-Syn) were purified and analyzed for their phosphorylation, cytotoxicity and seeding activity. ⋯ In vivo experiments showed that mice receiving intrastriatal inoculation of MSA-O-α-Syn developed more severe motor dysfunction and dopaminergic degeneration than mice receiving intrastriatal inoculation of PD-O-α-Syn. Compared with the mice inoculated with PD-O-α-Syn, the mice inoculated with MSA-O-α-Syn accumulated more phosphorylated and oligomerized α-Syn in the striatum and brain regions (substantia nigra, hippocampus and prefrontal cortex) away from the inoculated site. The results obtained suggest that α-Syn oligomers formed in PD and MSA plasma are different in phosphorylation, cytotoxicity, and seeding activity.
-
Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. ⋯ Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals.
-
Puberty is a sensitive developmental period during which stressors can cause lasting brain and behavioural deficits. While the acute effects of pubertal lipopolysaccharide (LPS) and antimicrobial (AMNS) treatments are known, their enduring impacts on neurodegeneration-related mechanisms and behaviours remain unclear. This study examined these effects in male and female mice. ⋯ Additionally, males treated with either LPS or AMNS had lower glial-derived neurotrophic factor receptor alpha-1 (GFRA1) expression in the primary motor cortex (M1) than females. Mice treated with LPS alone had decreased GFRA1 expression in the DG and decreased S1R expression in the secondary motor cortex (M2). These findings suggest that pubertal AMNS and LPS treatments may lead to enduring changes in biomarkers and behaviours related to neurodegeneration.
-
This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. ⋯ This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.
-
Short-term synaptic plasticity refers to the regulation of synapses by their past activity on time scales of milliseconds to minutes. Hippocampal mossy fiber synapses onto CA3 pyramidal cells (Mf-CA3 synapses) are endowed with remarkable forms of short-term synaptic plasticity expressed as facilitation of synaptic release by a factor of up to ten-fold. Three main forms of short-term plasticity are distinguished: 1) Frequency facilitation, which includes low frequency facilitation and train facilitation, operating in the range of tens of milliseconds to several seconds; 2) Post-tetanic potentiation triggered by trains of high frequency stimulation, which lasts several minutes; 3) Finally, depolarization-induced potentiation of excitation, based on retrograde signaling, with an onset and offset of several minutes. ⋯ We then review evidence for a physiological function of short-term plasticity of Mf-CA3 synapses in information transfer between the dentate gyrus and CA3 in conditions of natural spiking, and discuss how short-term plasticity counteracts robust feedforward inhibition in a frequency-dependent manner. Although DG-CA3 connections have long been proposed to play a role in memory, direct evidence for an implication of short-term plasticity at Mf-CA3 synapses is mostly lacking. The mechanistic knowledge gained on short-term plasticity at Mf-CA3 synapses should help in designing future experiments to directly test how this evolutionary conserved feature controls hippocampal circuit function in behavioural conditions.