Neuroscience
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Depression has huge social risks of high incidence, disability, and suicide. Its prevalence and harm in people with hyperglycemia are 2-3 times higher than in normal people. However, antidepressants with precise curative effects and clear mechanisms for patients with hyperglycemia are currently lacking. ⋯ Catalpol also reversed the abnormal phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the abnormal levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein, heme oxygenase-1 (HO-1), and antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and malondialdehyde in the hippocampus and frontal cortex of STZ-induced hyperglycemic mice. Thus, catalpol attenuates depressive-like behavior in pathological hyperglycemic state, and the antidepressant mechanism could at least be partly attributed to the upregulation of the PI3K/AKT/Nrf2/HO-1 signaling pathway in both brain regions, thus restoring the balance between oxidative and antioxidant damage. These data expanded the scientific understanding of catalpol and provided preclinical experimental evidence for its application.
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The role of anti-inflammatory cytokines in the mechanisms of learning and memory, modulation of synaptic plasticity in the mammalian brain has not received sufficient attention. These issues are discussed in this review, and among the many cytokines, attention is paid to the most studied in this respect IL-10, IL-4, IL-13 and TGF-β. The level of anti-inflammatory cytokines in the brain tends to increase during memory acquisition, but the significance of such an increase is unclear. ⋯ It has also been shown that TGF-β is able to optimize late stage LTP in the hippocampus and support the consolidation of memory traces in behavioral studies. Cytokines have an effect on learning and memory through their influence on neuroplasticity, neurogenesis in the hippocampus and regulation of the neurovascular unit. Experiments have shown such an effect, and the data obtained create the prerequisites for new therapeutic approaches to the correction of cognitive impairments.
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In many species, social communication and mate choice are influenced by olfactory cues associated with the major histocompatibility complex (MHC). It has been reported that humans also respond to olfactory signals related to the human MHC-equivalent, the Human Leucocyte Antigen (HLA)-System, and exhibit an olfactory-mediated preference for potential mating partners with a dissimilar, disassortative, HLA-type compared to their own. The aim of this study was to investigate whether HLA-associated peptides, presented as volatile cues, elicit neuronal responses at the receptors in the human olfactory epithelium and can be consciously perceived. ⋯ Furthermore electro-olfactograms of the olfactory epithelium and EEG-derived chemosensory event related potentials were recorded using precisely controlled olfactometric stimulation with peptides and control odors. Based on responses from 52 young, healthy participants the peptides could not be discriminated and the electrophysiological signals provided no evidence for a specific response to the peptides which was in contrast to the control odors. In conclusion, within the current setup the results suggest that HLA-associated peptides do not produce specific olfactory activation in humans.
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Exposure to intense or repeated stressors can lead to depression or post-traumatic stress disorder (PTSD). Neurological changes induced by stress include impaired neurotrophin signaling, which is known to influence synaptic integrity and plasticity. The present study used an ex vivo approach to examine the impact of acute or repeated stress on BDNF-stimulated TrkB signaling in hippocampus (HIPPO) and prefrontal cortex (PFC). ⋯ Three key findings are (1) exposure to stressors significantly diminished BDNF-stimulated TrkB signaling in HIPPO and PFC such that reductions in TrkB activation, diminished recruitment of adaptor proteins to TrkB, reduced activation of downstream signaling molecules, disruption of TrkB-NMDAr linkage, and changes in basal and BDNF-stimulated Arc expression were observed. (2) After stress, BDNF stimulation enhanced TrkB-NMDAr linkage in PFC, suggestive of compensatory mechanisms in this region. (3) We discovered an uncoupling between TrkB signaling, TrkB-NMDAr linkage and Arc expression in PFC and HIPPO. In addition, a robust surge in pro-inflammatory cytokines was observed in both regions after repeated exposure to stressors. Collectively, these data provide therapeutic targets for future studies that investigate how to reverse stress-induced downregulation of BDNF-TrkB signaling and underscore the need for functional studies that examine stress-related TrkB-NMDAr activities in PFC.
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The placenta is the primary source of serotonin (5-HT) for fetal development, programming fetal neural wiring in humans and other mammals. The fluctuation in maternal 5-HT affects fetal neurogenesis with life-long consequences, however, its mechanisms have not been well known. The chicken embryo, independent of maternal neurohormonal influence, may offer an ideal model for studying the mechanisms of prenatal 5-HT exposure altering postnatal physiological homeostasis and behavioral exhibition. ⋯ The comprehensive effect of 5-HT exposure was not dosage-dependent but the working pathways differed, 10 µg 5-HT exposure reduced 5-HT turnover rate, increased 5-HT 1a receptor expression, and facilitated the ventral tegmental area neuronal development; while 20 µg 5-HT exposure increased the serotoninergic and DAergic neurotransmission and enhanced serotoninergic regulation to the hypothalamus. These findings indicate that the 5-HT exposure effect can be achieved via different paths by modifying the embryonic serotonergic (5-HTergic) and DAergic systems and altering fetal 5-HTergic influence on the thalamocortical circuit and hypothalamic-pituitary-adrenal axis. These results may offer a novel sight for understanding the function of 5-HT during neurodevelopment and raise the possibility for using selective 5-HT reuptake inhibitors to regulate emotional and mental wellness during early pregnancy and possible risks of complications for babies.