Neuroscience
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Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies showed higher startle amplitudes and exaggerated fear reactivity to unpredictable vs. predictable threats in individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS studies use both sexes, a surprisingly limited number of rodent FPS studies use females. ⋯ However, in the classic FPS, Sprague-Dawley females show reduced proportion between cued fear and cue-elicited vigilant state than males. Lastly, a prominent sex difference is uncovered following unpredictable fear-conditioning (cue and shock un-paired), with Wistar, but not Sprague-Dawley, females showing significantly higher startle overall during the FPS recall, regardless of trial type, and higher contextual fear than males. This striking sex difference in processing unpredictable threats in rodent FPS might help to understand the mechanisms underlying higher incidence of PTSD in women.
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Accumulation of white adipose tissue (WAT) during obesity is associated with the development of chronic low-grade inflammation, a biological process known as lipoinflammation. Systemic and central lipoinflammation accumulates pro-inflammatory cytokines including IL-6, IL-1β and TNF-α in plasma and also in brain, disrupting neurometabolism and cognitive behavior. ⋯ This review will provide experimental and clinical evidence supporting the contribution of obesity- or overnutrition-related lipoinflammation affecting the mesocorticolimbic reward circuit and enhancing food reward responses. We will also address neuroanatomical targets of inflammatory profiles that modulate food reward responses during obesity and describe potential cellular and molecular mechanisms of overnutrition linked to addiction-like behavior favored by brain lipoinflammation.
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The ventromedial hypothalamic nucleus (VMN) controls glucose counter-regulation, including pituitary growth hormone (GH) secretion. VMN neurons that express the transcription factor steroidogenic factor-1/NR5A1 (SF-1) participate in glucose homeostasis. Research utilized in vivo gene knockdown tools to determine if VMN growth hormone-releasing hormone (Ghrh) regulates hypoglycemic patterns of glucagon, corticosterone, and GH outflow according to sex. ⋯ Ghrh gene knockdown altered Ghrh/SF-1 neuron estrogen receptor-alpha (ERα) and ER-beta transcripts in hypoglycemic male, not female rats, but up-regulated GPR81 lactate receptor mRNA in both sexes. Outcomes infer that VMNdm Ghrh/SF-1 neurons may be an effector of SF-1 control of counter-regulation, and document Ghrh modulation of hypoglycemic patterns of glucose-regulatory neurotransmitter along with estradiol and lactate receptor gene transcription in these cells. Co-transmission of glucose-inhibitory and -stimulatory neurochemicals of diverse chemical structure, spatial, and temporal profiles may enable VMNdm Ghrh neurons to provide complex dynamic, sex-specific input to the brain glucose-regulatory network.
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Intranasal insulin reduces lesion size and enhances memory capacity in traumatic brain injury (TBI) models, but the molecular mechanisms behind this neuroprotective action not yet understood. Here we used Feeney's free-falling method to construct TBI mouse models and administrated intranasal insulin, rapamycin, insulin and rapamycin, or normal saline to assess their effects on neurological functions, cerebral edema, and the expression of Iba1 in microglia through immunofluorescence assay. We also measured concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brain using enzyme immunosorbent assay, investigated apoptosis with TUNEL staining and Western blotting, and evaluated autophagy, endoplasmic reticulum (ER) stress, and PI3K/Akt/mTOR signaling pathway with Western blotting. ⋯ TUNEL assay and Western blotting also indicated that intranasal insulin inhibited ER stress-mediated apoptosis. Interestingly, the mTOR inhibitor rapamycin partially blocked the pro-autophagy and anti-apoptosis effects of intranasal insulin both on days 1 and 3 post TBI. Our results suggest that intranasal insulin can ameliorate TBI by regulating autophagy and ER stress-mediated apoptosis through the PI3K/AKT/mTOR signaling pathway, providing a promising therapeutic strategy for TBI.