Neuroscience
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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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Ischemic stroke (IS) is one of the leading causes of disability and death worldwide. Long-chain fatty-acid-coenzyme A ligase 4 (ACSL4) is a critical isozyme for ferroptosis that participates in the progression of IS. RING finger protein 146 (RNF146) is an E3 ligase predicted to interact with ACSL4 and regulated by activating transcription factor 3 (ATF3). ⋯ RNF146 overexpression could prevent the stimulation of OGD/R-induced LDH, MDA, and Fe2+ levels and ferroptosis-related gene expression. ATF3 could activate the transcription and expression of RNF146, leading to the inhibition of OGD/R-induced neuron ferroptosis. The ATF3-mediated RNF146 could alleviate neuronal damage in IS by regulating ACSL4 ubiquitination and ferroptosis, providing a novel theoretical basis for exploring therapeutic targets and strategies.
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While the functional and behavioral role of the medial habenula (MHb) is still emerging, recent data indicate an involvement of this nuclei in regulating mood, aversion, and addiction. Unique to the MHb is a large cluster of cholinergic neurons that project to the interpeduncular nucleus and densely express acetylcholine receptors (AChRs) suggesting that the activity of these cholinergic neurons may be regulated by ACh itself. Whether endogenous ACh from within the habenula regulates cholinergic neuron activity has not been demonstrated. ⋯ To test this hypothesis, we expressed channelrhodopsin in a portion of MHb cholinergic neurons while recording from non-opsin-expressing neurons. Light pulses progressively increased activity of MHb cholinergic neurons indicating feed-forward activation driven by MHb ACh release. These data indicate MHb cholinergic neurons may utilize a unique feed-forward mechanism to synchronize and increase activity by releasing local ACh.
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Cerebral ischemia is one of the major problems threatening global health. Many of the cerebral ischemia survivors would suffer from the physical and cognitive disabilities for their whole lifetime. Cell based-therapies have been introduced as a therapeutic approach for alleviating ischemia-enforced limitations. ⋯ GAP-43 showed significant protein expression in microglia + pericytes and microglia M2 + pericytes groups compared to the control group. Conversely, IL-1 levels diminished in all of the pericytes microglia + pericytes, and microglia M2 + pericytes groups compared to the ischemic controls. Current study highlights efficiency of M2 microglia and pericytes combinatory transplantation therapeutic role on relieving ischemic stroke outcomes.
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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.