Seizures induce c-fos expression in a subset of astrocytes, termed fostrocytes, that dampen subsequent seizures
- 1University of Virginia
Abstract
Objective: The original goal was to map neuronal circuits activated by spontaneous seizures in models of temporal lobe epilepsy. Studies used the c-fos driven TRAP2 system, which has been used successfully to label neurons after seizures. Unexpectedly, astrocytes were also labeled, then shown to express c-fos in a sustained manner after seizures. The role of these so-called fostrocytes in spontaneous seizures was studied using novel Cre-dependent AAVs. Methods: Studies used a homozygous mouse line produced by crossing TRAP2 Cre-driver mice with the Ai9 Cre-reporter line. Seizures were induced using electrical stimulation, kainic acid, or pilocarpine. Cre-dependent AAVs used the GFAP promoter to drive expression of either the catalytic A chain of diphtheria toxin (DTA), GFP, or empty vector. Spontaneous seizures were continuously recorded using EEG. Results: Discrete seizures in naive mice evoked transient c-fos expression in all astrocytes, while status epilepticus evoked a higher and sustained level of c-fos expression. Timing the activation of the TRAP2 system allowed specific labeling of the subset of astrocytes with high c-fos expression. These cells were colocalized with established astrocyte markers, showed reactive astrocyte morphology, and were selectively labeled by GFAP-driven Cre-dependent AAVs. Ablation of fostrocytes in spontaneously seizing mice increased seizure frequency. Significance: Next-generation sequencing studies have revealed a great diversity of astrocyte subtypes, identifying clusters with up-regulated c-fos expression in patients with neurological disorders. In conclusion, these studies suggest that therapies that augment the activity of c-fos expressing astrocytes would have anti-seizure activity.
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BibTeX
@misc{failor2026seizures,
title = {{Seizures induce c-fos expression in a subset of astrocytes, termed fostrocytes, that dampen subsequent seizures}},
author = {M. J. Failor and B. P. Bork and J. M. San Pietro and A. Maciejczuk and K. Elmer and C. Lile-King and M. Oliinyk and J. L. Choi and A. H. Huang and D. J. Tabor and R. P. Gaykema and E. Perez-Reyes},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748637},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748637v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Seizures induce c-fos expression in a subset of astrocytes, termed fostrocytes, that dampen subsequent seizures
AU - M. J. Failor
AU - B. P. Bork
AU - J. M. San Pietro
AU - A. Maciejczuk
AU - K. Elmer
AU - C. Lile-King
AU - M. Oliinyk
AU - J. L. Choi
AU - A. H. Huang
AU - D. J. Tabor
AU - R. P. Gaykema
AU - E. Perez-Reyes
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748637
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748637v1
AB - Objective: The original goal was to map neuronal circuits activated by spontaneous seizures in models of temporal lobe epilepsy. Studies used the c-fos driven TRAP2 system, which has been used successfully to label neurons after seizures. Unexpectedly, astrocytes were also labeled, then shown to express c-fos in a sustained manner after seizures. The role of these so-called fostrocytes in spontaneous seizures was studied using novel Cre-dependent AAVs. Methods: Studies used a homozygous mouse line produced by crossing TRAP2 Cre-driver mice with the Ai9 Cre-reporter line. Seizures were induced using electrical stimulation, kainic acid, or pilocarpine. Cre-dependent AAVs used the GFAP promoter to drive expression of either the catalytic A chain of diphtheria toxin (DTA), GFP, or empty vector. Spontaneous seizures were continuously recorded using EEG. Results: Discrete seizures in naive mice evoked transient c-fos expression in all astrocytes, while status epilepticus evoked a higher and sustained level of c-fos expression. Timing the activation of the TRAP2 system allowed specific labeling of the subset of astrocytes with high c-fos expression. These cells were colocalized with established astrocyte markers, showed reactive astrocyte morphology, and were selectively labeled by GFAP-driven Cre-dependent AAVs. Ablation of fostrocytes in spontaneously seizing mice increased seizure frequency. Significance: Next-generation sequencing studies have revealed a great diversity of astrocyte subtypes, identifying clusters with up-regulated c-fos expression in patients with neurological disorders. In conclusion, these studies suggest that therapies that augment the activity of c-fos expressing astrocytes would have anti-seizure activity.
ER -