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Neural Activation and Social Stress Linked to a Novel Genetic Mechanism

by Karishma Abhishek on Oct 14 2021 8:41 AM

Neural Activation and Social Stress Linked to a Novel Genetic Mechanism
Neural excitation/activation and social stress in the brain may induce a novel post-translational modification – protein lactylation as per a study “Protein lactylation induced by neural excitation”, at The Fujita Health University, published in the journal Cell Reports.
Protein lactylation (lysine lactylation) is one of the recently discovered post-translational modification of protein. It involves the addition of a lactyl group to lysine residues. The study team explored this concept in brain cells.

Novel Post-Translational Modification in Brain

The study reveals the positive link between protein lactylation in neurons and the lactate levels (especially lactylation of H1 histones) in mice through biochemistry, cell culture, histology, and mouse behavior experiments.

The link was further enhanced by neural excitation and social stress, especially in the prefrontal cortex (PFC) in vivo. Lactate or lactic acid is an end-product of a pathway (glycolytic pathway) that increases along with energy demand (e.g., after exercise).

However, the higher levels of lactate have also been noted in multiple neuropsychiatric disorders, such as bipolar disorder, schizophrenia, major depression, & anxiety disorders.

Lactate is noted to have an antidepressant effect. Moreover, chronically elevated brain lactate levels may serve as a compensatory mechanism against stress.

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“The lactate-sensitive epigenetic changes in the context of stress may play a role in gene-mediated regulation of behavior. However, for now, these data remain entirely correlational. It is important to provide mechanistic insights on how histone lactylation may affect stress-related responses. We are currently conducting experiments to address the issue,” says Dr. Hideo Hagihara, lead author of the paper.

Source-Medindia


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