# Signaling mechanisms underlying epilepsy and autism comorbidity

> **NIH NIH R15** · BAYLOR UNIVERSITY · 2022 · $343,235

## Abstract

One of the most susceptible periods in life to experience seizures is during the neonatal period.
Seizures during this sensitive period can result in cognitive and behavioral impairments later in
life. Specifically, early life seizures have shown to lead to the development of autistic-like
behaviors. There have been many proposed mechanisms that describe the changes to the brain
following seizures that have led to important advancements regarding therapeutics for epilepsy.
However, approximately one third of individuals with epilepsy are resistant to pharmaceutical
treatment options. Both inflammatory processes and the PI3K/AKT/mTOR pathway have been
shown to play a role in the comorbidities associated with epilepsy, specifically autistic-like
behavior. However, how the immune system and the mTOR signaling cascade interact to
contribute to seizures and subsequent behavioral impairments is unknown.
This study will investigate the mechanistic link between seizures during the neonatal period and
the development of autistic-like behavior in mice. On postnatal day (PD) 10, male and female
C57BL/6J mice will be given kainic acid to induce status epilepticus followed by administration
of minocycline, rapamycin, or a combined treatment of both, one hour and 24 hours following
status epilepticus. On PD12 and PD15, tissue will be collected for hippocampal cytokine
analysis with RT-qPCR, Western blotting with hippocampal and cortical tissue to examine
proteins in the PI3K/AKT/mTOR pathway, and immunohistochemistry to examine changes in
astrocyte and microglia reactivity. A separate cohort of mice will go through the same early life
seizure and treatment paradigm on PD10 and PD11, followed by examination of autistic-like
behavioral changes. We will examine changes in communication, social behavior, repetitive
behavior, learning and memory, anxiety, locomotor activity, and electrographic activity. The
impact of minocycline, rapamycin, and the combined treatment on autistic-like behavior will help
elucidate a possible mechanism for how characteristics of those with autism develop following
early life seizures. Inhibiting the neuroinflammatory component of seizures could serve as an
alternative treatment for those that suffer from seizures early in life, with hopes to minimize long-term behavioral comorbidities and epilepsy.

## Key facts

- **NIH application ID:** 10358673
- **Project number:** 2R15NS088776-03
- **Recipient organization:** BAYLOR UNIVERSITY
- **Principal Investigator:** JOAQUIN N LUGO
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $343,235
- **Award type:** 2
- **Project period:** 2021-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358673

## Citation

> US National Institutes of Health, RePORTER application 10358673, Signaling mechanisms underlying epilepsy and autism comorbidity (2R15NS088776-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358673. Licensed CC0.

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