ArticleFrontiers in cellular neuroscience2022
Leucine mediates cognitive dysfunction in early life stress-induced mental disorders by activating autophagy.
Article in Frontiers in cellular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Trial
- An Anthocyanin- and Anti-Ageing Amino Acids-Enriched Pigmented Rice Innovation Promotes Healthy Ageing Through the Modulation of Telomere, Oxidative Stress and Inflammation Reduction: A Randomized Clinical Trial.International journal of molecular sciences · 2025Trial
- Ginsenoside Rg1 ameliorates lipopolysaccharide-induced depressive-like behaviors in mice by attenuating neuroinflammation and neuronal damage.Scientific reports · 2026Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Progress in Molecular Mechanisms of Depression Induced by Mother-Infant Separation and Intervention of Traditional Chinese Medicine.Alpha psychiatry · 2025Review
- Nutritional interventions to counteract the detrimental consequences of early-life stress.Molecular psychiatry · 2025Review
- Maternal Substance Use and Early-Life Adversity: Inducing Drug Dependence in Offspring, Interactions, Mechanisms, and Treatments.Addiction & health · 2024Review
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Authors and funding
11 authors at 1 institution.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: To explore the relationship between leucine in cerebrospinal fluid (CSF) and cognitive dysfunction in rats with early life stress (ELS) induced mental illness, and pathophysiological mechanism involved. Methods: The maternal separation (MS), an animal paradigm used widely as a preclinical model of ELS which is one of the important risk factors for mental disorders. Behavioral experiments including open-field test, sucrose preference, object recognition and Morris water maze tests, Nissl staining, transmission electron microscopy and WES were employed in the present study. Results: The behavioral results showed that MS rats were more prone to cognitive impairment and depression-and-anxiety-like behaviors than controls, including spatial self-exploration ability, memory ability, and spatial learning and memory function. Nissl staining analysis indicated that the number of neurons in the CA1 and CA3 regions of the hippocampus significantly decreased and the arrangement of nerve cells was abnormal. The leucine levels were decreased in the CSF of MS rats and highly correlated with the number of hippocampal neurons, and yet leucine supplementation improved the degree of MS-induced cognitive impairment. Furthermore, there were autophagosomes in the hippocampus of the low-leucine diet rats of the control and MS group but not in the high-leucine diet MS group by transmission electron microscopy. The protein expression of Beclin-1 in the hippocampus was significantly increased in the MS normal diet group and MS low-leucine diet group, yet decreased in the MS high-leucine diet group compared with the MS low-leucine diet group. Meanwhile, the Bcl-2/Bax ratio was significantly decreased in the control low-leucine diet group, MS normal diet group and MS low-leucine diet group. Ultimately, Conclusions: MS model caused adult male rats to be susceptible to cognitive dysfunction, which may regulate autophagy in hippocampal neurons through leucine metabolism in CSF.
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