Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy.
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R · 33 lines · 1.7 KB · no license · 1 match
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Overview
- Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Physiology, Pharmacology, and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Synaptic Plasticity Section, Cellular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, 69120 Heidelberg, Germany
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Institute of Medicine, University of Maine, Orono, ME 04469, USA
- Johns Hopkins University Kavli Neuroscience Discovery Institute, Baltimore, MD 21205, USA
- Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Abstract
A fundamental but unanswered question in neuropsychiatry is whether the psychiatric symptoms of epilepsy are caused by the same or a separate pathophysiology as seizures. To address this question, we investigated a monogenic form of epilepsy (pyridoxine-dependent epilepsy) caused by aldehyde dehydrogenase 7 family member A1 (ALDH7A1) mutations. ALDH7A1 global knockout mice exhibited both seizure-associated and maladaptive affective behavioral phenotypes. However, seizure phenotypes were caused by ALDH7A1 deletion in hepatocytes whereas maladaptive affective behaviors were caused by ALDH7A1 deletion in astrocytes. Deletion in astrocytes disrupted astrocyte redox homeostasis, impairing regulation of extracellular ion concentrations and reducing neuronal activity in the prelimbic cortex. Sulforaphane, which activates the NRF2 antioxidant pathway, restored prelimbic neuronal activity and rescued maladaptive affective behaviors in ALDH7A1 knockout mice but did not prevent seizures. These studies implicate astrocyte redox homeostasis and prelimbic hypoactivity in maladaptive affective behavioral phenotypes in a congenital form of epilepsy, which are mechanistically and therapeutically dissociable from seizure pathophysiology.
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KunYang99/ALDH7A1
07feee5b0c8d90e8ca6e4c169a1563a9b3f0327c, 16 June 2026Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
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Zenodo 20719402
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
- 27 September 2026: the link answers (HTTP 200)
5 files
- CIE/
bin/ — R, 670 linesmycie.R - run_CIE.R — R, 33 lines
- run_GSEA.sh — Shell, 7 lines
- run_deseq.R — R, 17 lines
- README.md — Text, 12 lines
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Data
Datasets cited
- geo:GSE328106 — at NCBI GEO; found in “Data, code, and materials availability:”
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- ncbi.nlm.nih.gov/
geo — NCBI; found in “Data, code, and materials availability:”
Data, code, and materials availability
The RNA-seq expression data are available at the NCBI Gene Expression Omnibus (GEO; https://
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 23 authors, 15 MeSH terms, 2 funders, 122 references, 26 RRIDs.
Cite
This paper
Faust, T. E., Saito, A., Ishikawa, S., Yang, K., Xin, W., Namkung, H., Agarwal, A., Ramos, A., Lee, B. J., Hayes, L., Srivastava, R., Adelakun, S., Saha, S., Palen, T., Cash-Padgett, T., Wood, D. J., Carloni, E., Yusa, R., Jaaro-Peled, H., . . . Sawa, A. (2026). Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy. Science advances, 12(31), eaef6777. https://
BibTeX
@article{faust2026astroc
author = {Faust, Travis E and Saito, Atsushi and Ishikawa, Shoichi and Yang, Kun and Xin, Wendy and Namkung, Ho and Agarwal, Amit and Ramos, Adriana and Lee, Brian J and Hayes, Lindsay and Srivastava, Rupali and Adelakun, Sunday and Saha, Sneha and Palen, Trexy and Cash-Padgett, Tyler and Wood, Daniel J and Carloni, Elisa and Yusa, Ryosuke and Jaaro-Peled, Hanna and Fahey, Jed W and Bergles, Dwight E and Ishizuka, Koko and Sawa, Akira},
title = {{Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy}},
journal = {Science advances},
year = {2026},
month = jul,
volume = {12},
number = {31},
pages = {eaef6777},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/
url = {https://
pmid = {42525741},
pmcid = {PMC13418531}
}
RIS
TY - JOUR
AU - Faust, Travis E
AU - Saito, Atsushi
AU - Ishikawa, Shoichi
AU - Yang, Kun
AU - Xin, Wendy
AU - Namkung, Ho
AU - Agarwal, Amit
AU - Ramos, Adriana
AU - Lee, Brian J
AU - Hayes, Lindsay
AU - Srivastava, Rupali
AU - Adelakun, Sunday
AU - Saha, Sneha
AU - Palen, Trexy
AU - Cash-Padgett, Tyler
AU - Wood, Daniel J
AU - Carloni, Elisa
AU - Yusa, Ryosuke
AU - Jaaro-Peled, Hanna
AU - Fahey, Jed W
AU - Bergles, Dwight E
AU - Ishizuka, Koko
AU - Sawa, Akira
TI - Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/
VL - 12
IS - 31
SP - eaef6777
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/
UR - https://
LA - en
ER -
CSL-JSON
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