Neuroscience
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Astrocytes and microglia appear central to the initiation and progression of neuroinflammation in Alzheimer's disease (AD). In this study, inflammation was mimicked by Aβ1-42 treatment of rat astrocytes (RA) and N9 microglia cell lines. Inflammation induced by Aβ1-42 can be inhibited by pyrrolidine dithiocarbamic acid (PDTC), indicating that the NF-κB signal pathway is involved in inflammation. ⋯ In addition, Res decreased the nuclear translocation of NF-κB/p65 when checked by immunofluorescence. Furthermore, Res increased the expression of NF-κB/p65 and decreased the expression of p-IκB in the cytoplasm in both RA and N9 microglia. Taken together, the present data indicate that Res reduces inflammation in RA and N9 microglia, and the anti-NF-κB signal pathway may be one of the target mechanisms.
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Stress is an adaptive and coordinated response to endogenous or exogenous stressors that pose an unpleasant and aversive threat to an individual's homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and cortisol in humans, are adrenal steroids which are released in response to stressful stimuli. Although they help individuals to cope with stress, their overexposure in animals has been implicated in hippocampal dysfunction and neuronal loss. ⋯ OT was unable to protect primary hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These results indicate that OT has inhibitory effects on CORT-induced neuronal death in primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic potential of OT in the treatment of stress-related disorders.
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Distinguishing between familiar and unfamiliar individuals is an important task that shapes the expression of social behavior. As such, identifying the neural populations involved in processing and learning the sensory attributes of individuals is important for understanding mechanisms of behavior. Catecholamine-synthesizing neurons have been implicated in sensory processing, but relatively little is known about their contribution to auditory learning and processing across various vertebrate taxa. ⋯ The pattern of EGR-1 expression in the locus coeruleus was similar to that observed in two auditory processing areas implicated in auditory learning and memory, namely the caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting a contribution of catecholamines to sensory processing. Consistent with this, the pattern of catecholaminergic innervation onto auditory neurons co-varied with the degree to which song playback affected the relative intensity of EGR-1 expression. Together, our data support the contention that catecholamines like norepinephrine contribute to social recognition and the processing of social information.
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Phosphorylation of α-synuclein at serine 129 (P-Ser 129 α-syn) is involved in the pathogenesis of Parkinson's disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quantitative relation of P-Ser 129 α-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brain areas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing a modeling-recovery-remodeling strategy. ⋯ P-Ser 129 α-syn aggregations or LB-like pathology was also found in the midbrain and the neocortex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cells surrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 α-syn negative. The findings of LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest that the modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investigations into the pathogenesis of PD and potential therapeutic development.
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Parkinson's disease (PD) related to homozygous mutations in the Pink1 gene is associated with nigrostriatal dopamine depletion and a wide range of sensorimotor deficits. In humans and animal models of PD, not all sensorimotor deficits are levodopa-responsive. We hypothesized that the underlying mechanisms of locomotion, limb control, and vocal communication behavior include other pathologies. ⋯ Pearson's correlations showed that increases in time to traverse a tapered balance beam are significantly associated with reductions in striatal dopamine. Ultrasonic vocalization complexity was positively correlated with LC norepinephrine concentrations. These data support the evolving hypothesis that differences in neural substrates and early-onset noradrenergic mechanisms in the brainstem may contribute to pathogenesis in the Pink1 -/- rat.