Journal
BIOMEDICINES
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines11010104
Keywords
growth hormone-releasing hormone; anxiolytic drug candidates; cognitive improvement; epigenetic modifications
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Neurodegenerative diseases involve changes in cognition, anxiety and autism-like behaviors, which are affected by epigenetic alterations. This study found that L-serine administration in GHRH-KO mice improved anxiety symptoms and behavioral deficits, while upregulating epigenetic markers and mRNA expression related to anxiety, cognition and autism-like behaviors. These findings offer new insights into the beneficial effects of L-serine intervention on neuropsychological impairments.
Neurodegenerative diseases feature changes in cognition, and anxiety-like and autism-like behaviors, which are associated with epigenetic alterations such as DNA methylation and histone modifications. The amino acid L-serine has been shown to have beneficial effects on neurological symptoms. Here, we found that growth hormone-releasing hormone knockout (GHRH-KO) mice, a GH-deficiency mouse model characterized by extended lifespan and enhanced insulin sensitivity, showed a lower anxiety symptom and impairment of short-term object recognition memory and autism-like behaviors. Interestingly, L-serine administration exerted anxiolytic effects in mice and ameliorated the behavioral deficits in GHRH-KO. L-serine treatment upregulated histone epigenetic markers of H3K4me, H3K9ac, H3K14ac and H3K18ac in the hippocampus and H3K4me in the cerebral cortex in both GHRH-KO mice and wild type controls. L-serine-modulated epigenetic marker changes, in turn, were found to regulate mRNA expression of BDNF, grm3, foxp1, shank3, auts2 and marcksl1, which are involved in anxiety-, cognitive- and autism-like behaviors. Our study provides a novel insight into the beneficial effects of L-serine intervention on neuropsychological impairments.
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