Maternal stress induced autophagy dysfunction and immune activation in the hippocampus of adolescence rat pups
Pornprom Surakul1, Nuanchan Chutabhakdikul2, Rapeepun Vanichviriyakit3
1Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand; Department of Physical Therapy, Faculty of Allied Health Sciences, Burapha University, Chon Buri 20131, Thailand.
Insights
Maternal stress in rats impairs autophagy and activates neuroinflammation, potentially explaining the link between early life stress and later neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Psychology
- Molecular Biology
Background:
- Maternal stress (MS) impacts fetal brain development, increasing offspring's risk for neuropsychiatric diseases.
- The precise mechanisms linking early-life stress to these disorders remain unclear.
- Neuroinflammation and autophagy dysfunction are implicated in psychiatric disorder pathology.
Purpose of the Study:
- To investigate the effects of maternal stress on autophagy and neuroimmune responses in the hippocampus of rat pups.
- To explore the potential role of corticosterone in mediating these stress-induced changes.
Main Methods:
- Maternal stress was induced in rats, and the hippocampus of offspring was analyzed for autophagy biomarkers (LC3B-II) and neuroinflammatory markers (IL-6, IL-10) across different developmental stages.
- In vitro studies used SH-SY5Y cells treated with corticosterone (CORT) and/or mycophenolic acid (MPA) to assess autophagy and inflammatory responses.
Main Results:
- Maternal stress led to a sustained decrease in LC3B-II and increased IL-6 and IL-10 levels in the rat pup hippocampus from adolescence into adulthood.
- Corticosterone treatment in vitro reduced LC3B-II and elevated IL-6 and IL-10.
- Autophagy suppression by MPA exacerbated IL-6 and IL-10 increases in corticosterone-treated cells.
Conclusions:
- Maternal stress induces long-term autophagy dysfunction and neuroinflammation in offspring brains.
- Corticosterone-induced autophagy impairment may activate the neuroimmune response.
- These findings suggest a potential mechanism linking maternal stress, autophagy, and neuroinflammation to neuropsychiatric disorders.
Abstract:
Maternal stress (MS) has long-term effects on fetal brain development and consequently increases the risk of neuropsychiatric diseases in the offspring, however, the mechanism that links between early life stress and subsequent neuropsychiatric diseases is still not clear. It is well known that both neuroinflammation and autophagy dysfunction contributes to the pathology of psychiatric disorders. We hypothesized that MS might alter autophagy function and activate the neuroimmune response in the pup's brain. To test this hypothesis, we investigated the effects of MS on the expression of the autophagy biomarker and neuroimmune response in the hippocampus of rat pups. Results revealed that MS-induced a long-term decrease of LC3B-II throughout the postnatal periods, together with an increase of IL-6 and IL-10 in the hippocampus of rat pups during adolescence. These changes lasted at least until adulthood. Results from the In vitro studies showed that a partially toxic dose of corticosterone (CORT) induced a significant decrease of LC3B-II, together with an increase of IL-6 and IL-10, in the SH-SY5Y cells. Moreover, suppression of autophagy by mycophenolic acid (MPA) leads to an increased IL-6 and IL-10 expression in the CORT-treated SH-SY5Y cells. Findings suggested that CORT decreased autophagy dysfunction could activate neuroimmune response in the SH-SY5Y cells. Results from this study provides initial evidence for the relationship between stress hormone, autophagy dysfunction, and neuroimmune activation, which may be the linking mechanism between early-life stress and subsequent neuropsychiatric disorders.
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