Dietary Phytochemicals Modulate Experience-Dependent Changes in Neurexin Gene Expression and Alternative Splicing in Mice after Chronic Variable Stress Exposure
Open accessAbstract
Neurexins (NRXNs) are cell-adhesion molecules important in the formation and remodeling of neural circuits. It has been shown that aversive environmental stimuli can affect the expression pattern of Neurexin genes (Nrxns) impacting the regulation of synaptic strength. Accumulated evidence suggests that, after chronic exposure to psychological stress, the triggered changes in gene expression and splicing patterns of Nrxns may be involved in aversive conditioning. Previously, we have demonstrated that a novel treatment using dietary phytochemicals can modulate the response to chronic variable stress (CVS) in mice. Here, we aimed to further investigate the long-term plasticity changes after CVS by focusing on the regulation of NRXNs at synapses. We found that CVS differentially triggers the region-specific gene expression of Nrxns in mice Nucleus Accumbens (NAc) and Hippocampus (HIPP). The prophylactic treatment with the combination of two phytochemicals dihydrocaffeic acid (DHCA) and Malvidin-3-O-glucoside (Mal-gluc) differentially modulated the stress-induced effects on Nrxn1 and 3 mRNA expression in these brain areas and promoted the alternative splicing of Nrxn3 in HIPP. Overall, our data supports the prophylactic effect of dietary phytochemicals in the restoration of stress-induced plasticity changes in mouse brain. By intervening in activity-dependent plasticity at synapses, these compounds may attenuate the effects of chronic aversive conditioning. We propose that an early therapeutic intervention may help with disorders of negative affect, such as depression or post-traumatic stress disorder. Our future studies will address how DHCA/Mal-gluc might serve as a potential complement for current therapies in depression and other mood disorders.
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [44]
Chronic psychological stress can alter Neurexin gene expression and splicing patterns, impacting synaptic strength regulation and potentially contributing to aversive conditioning.
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [44]
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [44]
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Shchaslyvyi, A. Y., Antonenko, S. V., & Telegeev, G. D. (2024) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph21081077 · Cited by 73 · see citing works
- Authors
- Freire-Cobo, C., & Wang, J.
- Affiliations
- James J. Peters VA Medical Center (US)
- ORCID
- Wang, Jun
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 883
- Pages
- 173362
- ISSN
- 0014-2999 (ISSN-L)
- PMC
- PMC7484199
- OpenAlex
- W3042925427
- Cited by
- 11
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2022: 2 · 2021: 2
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Complementary and Integrative Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dietary phytochemicals, neurexin, NRXN1, NRXN3, alternative splicing, chronic variable stress, dihydrocaffeic acid, malvidin-3-glucoside, nucleus accumbens, hippocampus, synaptic plasticity, aversive conditioning, depression, post-traumatic stress disorder, mood disorders, prophylaxis
- MeSH terms
- Animals, Anthocyanins, Behavior, Animal, Brain, Caffeic Acids, Calcium-Binding Proteins, Chronic Disease, Disease Models, Animal, Drug Therapy, Combination, Female, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Stress, Psychological, Synapses, Alternative Splicing, Neural Cell Adhesion Molecules, Phytochemicals
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