# Investigating the pathological consequences of seizure-induced activation of the HPA axis

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2021 · $360,938

## Abstract

Project Summary
 It is widely-accepted by both clinicians and basic scientists that stress can trigger and worsen seizures
in animal models and in patients with epilepsy through the actions of stress mediators. The body's
physiological response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis. The majority of
studies investigating the relationship between the HPA axis and epilepsy focus on the role of stress and the
proconvulsant actions of corticosterone (cortisol in humans) and corticotropin-releasing hormone (CRH).
Interestingly, our lab recently demonstrated that seizures themselves activate the HPA axis, forcing us to
reevaluate the role of the HPA axis in epilepsy. These findings suggest that seizure-induced activation of the
HPA axis may directly contribute to changes in seizure susceptibility. Further, hyperexcitability of the HPA axis
is a hallmark feature of depression, implicating seizure-induced activation of the HPA axis in the comorbidity of
depression and epilepsy. The overarching objective of the current study is to investigate the pathophysiological
consequences of this seizure-induced activation of the HPA axis, investigating the impact on the process of
epileptogenesis (Specific Aim 1), seizure activity in chronically epileptic mice (Specific Aim 2), and the role in
the comorbid depression (Specific Aim 3). These Aims will determine whether seizure-induced activation of the
HPA axis is culpable in worsening seizure activity, associated pathology, and depression-like behaviors in
chronically epileptic mice.

## Key facts

- **NIH application ID:** 10130005
- **Project number:** 5R01NS102937-05
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Jamie Lynn Maguire
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,938
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130005

## Citation

> US National Institutes of Health, RePORTER application 10130005, Investigating the pathological consequences of seizure-induced activation of the HPA axis (5R01NS102937-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130005. Licensed CC0.

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