Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats
Open accessAbstract
Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of ELS on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1 H MRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. MD was established in Sprague–Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1 H MRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Adult MD offspring exhibited depression-like behavior. Compared to the control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption ( p < 0.05). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1 H MRS, hippocampus of MD rats had elevated Glu and glutamate + glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln, γ-aminobutyric acid (GABA), and glutamate + glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1 H MRS-identified associations between Glu levels and ELS may guide future clinical studies.
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Glutamate and its receptors are associated with many neuropsychiatric illnesses, including depression.
“Glutamate and its receptors are associated with many neuropsychiatric illnesses, including depression.275,276”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [275]
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- Authors
- Guan, J., Ding, Y., Rong, Y., Geng, Y., Lai, L., Qi, D., Tang, Y., Yang, L., Li, J., Zhou, T., Wu, E., & Wu, R.
- Affiliations
- Shantou University (CN)
- Guangzhou Eighth People's Hospital (CN)
- Baylor Scott & White Medical Center - Temple (US)
- Zhengzhou University (CN)
- Texas A&M Health Science Center (US)
- Corresponding author
- Wu, Renhua
- ORCID
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-11-12
- Volume
- 11
- Issue
- 24
- Pages
- 4169-4178
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W3104161020
- Cited by
- 28
- References
- 56
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 10 · 2022: 4 · 2021: 5 · 2020: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- SSRN Electronic Journal (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Government of Guangdong Province (00218119101)
- Li Ka Shing Foundation (2020LKSFG05D)
- Department of Education of Guangdong Province (2015034)
- Shantou University (NTF10010)
- National Natural Science Foundation of China (30930027, 31870981, 60971075, 61902232, 82020108016)
- Natural Science Foundation of Guangdong Province (2015A030313444, S2011010005194)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- early life stress, maternal deprivation, glutamate metabolism, glutamate/glutamine, hippocampus, prefrontal cortex, depression-like behavior, anxiety-like behavior, cognitive impairment, GABA, sucrose preference, Morris water maze
- MeSH terms
- Animals, Behavior, Animal, Brain, Depression, Glutamine, Stress, Psychological, Rats, Sprague-Dawley, Glutamic Acid, Rats, Proton Magnetic Resonance Spectroscopy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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