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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The correlation of early life adversity with adulthood psychopathology has already been revealed by epidemiological studies. To find the biological mechanisms underlying the cross-talk between prenatal adversity and mental health, molecular genetic studies have been performed using animal models of prenatal undernutrition and stress, reporting altered expression of serotonin receptors which modulate the release of many neurotransmitters that regulate a broad range of physiological functions including psychopathology. Unfortunately, no such study has been possible on humans due to ethical reasons. ⋯ In a sex-stratified analysis, the pattern was only significant in females (p-value, 0.019) but not in males. We further tested the DNA methylation patterns specifically in HTR1A, HTR2A and the X-linked HTR2C and found reduced DNA methylation in females for HTR2A (p-value 0.033) and HTR2C (p-value 0.014) but not in males. Overall, this study reveals altered epigenetic regulation of the serotonin receptor signaling pathway in association with prenatal adversity in humans providing novel epigenetic evidence in support of neurodevelopmental origin of psychiatric disorders.
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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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Interleukin-33 (IL-33) is an inflammatory factor with an extensive range of biological effects and pleiotropic roles in diseases. Evidence suggests that IL-33 and its receptor ST2 play a pivotal role in chronic pain and itch at the level of primary sensory neurons, the spinal cord, and the brain. In this review, we outline an evolving understanding of the roles and mechanisms of IL-33 in chronic pathological pain, including inflammatory, neuropathic, and cancer, and chronic pruritus, such as allergic contact dermatitis, atopic dermatitis, and dry skin. Understanding the key roles of IL-33/ST2 signaling may provide exciting insights into the mechanisms of chronic pain and itch and lead to new clues for therapeutic approaches to the resolution of chronic pain and itch.