ArticleNeurobiology of stress
Hyper-excitability and epilepsy generated by chronic early-life stress.
Article in Neurobiology of stress. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- The multiple hit model of infantile and epileptic spasms: The 2025 update.Epilepsia open · 2025Article
- The evolving neurobiology of early-life stress.Neuron · 2025Review
- Early Life Stress Impairs VTA Coordination of BLA Network and Behavioral States.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The link between early-life adversity and later alcohol use disorder: A role for microglia?Neurobiology of stress · 2025Article
- A Computational Account of the Development and Evolution of Psychotic Symptoms.Biological psychiatry · 2025Review
- Article
- The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Rats Selected for Different Nervous Excitability: Long-Term Emotional-Painful Stress Affects the Dynamics of DNA Damage in Cells of Several Brain Areas.International journal of molecular sciences · 2024Article
- Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life.Biological psychiatry global open science · 2023Article
- Characterizing maternal isolation-induced ultrasonic vocalizations in a gene-environment interaction rat model for autism.Genes, brain, and behavior · 2023Article
- Cortical Parvalbumin-Positive Interneuron Development and Function Are Altered in the APC Conditional Knockout Mouse Model of Infantile and Epileptic Spasms Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.IBRO neuroscience reports · 2022Review
- Resource scarcity but not maternal separation provokes unpredictable maternal care sequences in mice and both upregulateNeurobiology of stress · 2022Article
- The effects of early life stress on impulsivity.Neuroscience and biobehavioral reviews · 2022Review
- Neurodevelopmental origins of substance use disorders: Evidence from animal models of early-life adversity and addiction.The European journal of neuroscience · 2022Review
- The neurobiology of childhood trauma, from early physical pain onwards: as relevant as ever in today's fractured world.European journal of psychotraumatology · 2022Review
- In Up to My Ears and Temporal Lobes: Effects of Early Life Stress on Epilepsy Development.Current topics in behavioral neurosciences · 2022Article
- Developmental Trajectories of Anhedonia in Preclinical Models.Current topics in behavioral neurosciences · 2022Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Epilepsy is more prevalent in populations with high measures of stress, but the neurobiological mechanisms are unclear. Stress is a common precipitant of seizures in individuals with epilepsy, and may provoke seizures by several mechanisms including changes in neurotransmitter and hormone levels within the brain. Importantly, stress during sensitive periods early in life contributes to 'brain programming', influencing neuronal function and brain networks. However, it is unclear if early-life stress influences limbic excitability and promotes epilepsy. Here we used an established, naturalistic model of chronic early-life stress (CES), and employed chronic cortical and limbic video-EEGs combined with molecular and cellular techniques to probe the contributions of stress to age-specific epilepsies and network hyperexcitability and identify the underlying mechanisms. In control male rats, EEGs obtained throughout development were normal and no seizures were observed. EEGs demonstrated epileptic spikes and spike series in the majority of rats experiencing CES, and 57% of CES rats developed seizures: Behavioral events resembling the human age-specific epilepsy infantile spasms occurred in 11/23 (48%), accompanied by EEG spikes and/or electrodecrements, and two additional rats (9%) developed limbic seizures that involved the amygdala. Probing for stress-dependent, endogenous convulsant molecules within amygdala, we examined the expression of the pro-convulsant neuropeptide corticotropin-releasing hormone (CRH), and found a significant increase of amygdalar--but not cortical--CRH expression in adolescent CES rats. In conclusion, CES of limited duration has long-lasting effects on brain excitability and may promote age-specific seizures and epilepsy. Whereas the mechanisms involved require further study, these findings provide important insights into environmental contributions to early-life seizures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.