Stress-Associated Molecular and Cellular Hippocampal Mechanisms Common for Epilepsy and Comorbid Depressive Disorders
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The review discusses molecular and cellular mechanisms common to the temporal lobe epileptogenesis/epilepsy and depressive disorders. Comorbid temporal lobe epilepsy and depression are associated with dysfunction of the hypothalamic-pituitary-adrenocortical axis. Excessive glucocorticoids disrupt the function and impair the structure of the hippocampus, a brain region key to learning, memory, and emotions. Selective vulnerability of the hippocampus to stress, mediated by the reception of glucocorticoid hormones secreted during stress, is the price of the high functional plasticity and pleiotropy of this limbic structure. Common molecular and cellular mechanisms include the dysfunction of glucocorticoid receptors, neurotransmitters, and neurotrophic factors, development of neuroinflammation, leading to neurodegeneration and loss of hippocampal neurons, as well as disturbances in neurogenesis in the subgranular neurogenic niche and formation of aberrant neural networks. These glucocorticoid-dependent processes underlie altered stress response and the development of chronic stress-induced comorbid pathologies, in particular, temporal lobe epilepsy and depressive disorders.
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Chronic stress results in neurodegeneration, loss of hippocampal neurons, and altered neurogenesis, contributing to the development of epilepsy and depressive disorders through shared molecular pathways.
“This results in neurodegeneration, loss of hippocampal neurons, and altered neurogenesis, contributing to the development of epilepsy and depressive disorders through shared molecular pathways involving neurotransmitters and neurotrophic factors [68].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [68]
Chronic stress leads to excessive glucocorticoid production, which disrupts hippocampal function.
“Chronic stress leads to excessive glucocorticoid production, which disrupts hippocampal function—a brain region critical for learning, memory, and emotional regulation.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [68]
Epilepsy and depression often co-occur, particularly in temporal lobe epilepsy, linked by dysfunction in the HPA axis.
“Epilepsy and depression often co-occur, particularly in cases of temporal lobe epilepsy, linked by dysfunction in the HPA axis.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [68]
The hippocampus's high functional plasticity makes it particularly vulnerable to stress-induced damage, mediated by glucocorticoid hormones.
“The hippocampus’s high functional plasticity makes it particularly vulnerable to stress-induced damage, mediated by glucocorticoid hormones.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [68]
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Self-citationLu, J. J., Huang, H., Zeng, Q., Zhang, X., Xu, M., Cai, Y., Wang, Q., Huang, Y., Peng, Q., & Deng, L. (2019) · Journal of Integrative Neuroscience · doi:10.31083/j.jin.2019.02.16 · Cited by 21 · see citing works
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Do certain signal transduction mechanisms explain the comorbidity of epilepsy and mood disorders?
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Chronically altered NMDAR signaling in epilepsy mediates comorbid depression
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D’Alessio, L., Konopka, H., Solis, P. C. L., Scévola, L., Lima, M. F., Nuñez, C., Seoane, E., Oddo, S. A., & Kochen, S. S. (2019) · Behavioural Neurology · doi:10.1155/2019/7396793 · Cited by 16 · see citing works
Gulyaeva, N. V. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15238 · Cited by 16 · see citing works
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Emotional-affektive, Angst- und Persönlichkeitsstörungen bei Epilepsien
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Aberrant neurogenesis in adult epileptic brain: compensatory or pathologic
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Factors associated with depression in people with epilepsy: a retrospective case-control analysis
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Physiological continuum of plasticity and pathology of the nervous system
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Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Pauli, E., and Stefan, H. (2009) Emotional and affective disorders, anxiety and personality disorders in epilepsies, Nervenarzt, 80, 1440 1451, doi: 10.1007/s00115 009 2740 2. · DOI
- Noebels, J. L., Avoli, M., Rogawski, M. A., Olsen, R. W., and Delgado Escueta, A. V., eds.) 4 th Edn., Bethesda (MD): National Center for Biotechnology Information (US). 112.
Cited by
Sorted by citations
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
- Gulyaeva, N. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Gulyaeva, Natalia V.
- ORCID
- Gulyaeva, Natalia V.
- Venue
- Biochemistry (Moscow)
- Publisher
- Pleiades Publishing Ltd
- Published
- 2021-05-26
- Volume
- 86
- Issue
- 6
- Pages
- 641-656
- ISSN
- 0006-2979 (ISSN-L)
- 1608-3040
- OpenAlex
- W3169798616
- Cited by
- 54
- References
- 123
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 8 · 2023: 13 · 2022: 6 · 2021: 5
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biochemistry (Moscow) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- temporal lobe epilepsy, depression, comorbidities, hippocampus, chronic stress, hypothalamic-pituitary-adrenal axis, glucocorticoids, glucocorticoid receptor, neuroinflammation, neurogenesis, neurodegeneration, stress response
- MeSH terms
- Animals, Depressive Disorder, Emotions, Epilepsy, Epilepsy, Temporal Lobe, Glucocorticoids, Hippocampus, Humans, Inflammation, Learning, Memory, Stress, Psychological
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