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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

Astrocyte-Associated ABCA1/APOE Responses Accompany Hippocampal Lipid Remodeling and Ectopic Neuronal Accumulation During Epileptogenesis.

  • Lu Chen1,2
  • Xiao-Rui Shi1,2
  • Jia-Yi Chen1,3
  • Ying-Ting Wang1,2
  • Le Du2,4
  • Yang Ni2
  • Jun-Min Chen1,2
  • An-Chen Guo1,2
  • Qian Wu5
  • Jian-Ping Wu2,6,7
  • Qun Wang1,2,8
8 affiliations
  1. 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  2. 2China National Clinical Research Center For Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  3. 3National-Local Joint Engineering Research Center For Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China.
  4. 4School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.
  5. 5Department of Neurology, First Affiliated Hospital, Kunming Medical University, Kunming, China.
  6. 6Beijing Key Laboratory of Drug and Device Research and Development for Cerebrovascular Diseases, Beijing, China.
  7. 7Department of Pharmacology, Hubei University of Medicine, Shiyan, China.
  8. 8Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Abstract

Temporal lobe epilepsy (TLE) is characterized by progressive hippocampal remodeling, including reactive astrogliosis and aberrant neuronal positioning. Although lipid disturbances are implicated in epileptogenesis, how astrocyte-associated lipid responses relate to hippocampal remodeling remains poorly understood. Here, human TLE and kainic acid (KA)-treated mouse transcriptomic datasets identified ATP-binding cassette transporter A1 (ABCA1)/Abca1 as a nominal astrocyte-associated candidate, while KA- and pilocarpine-induced status epilepticus (SE) elicited astrocyte-associated ABCA1/apolipoprotein E (APOE) responses. Ectopic granule cells and immature neurons accumulated in the hilus and were spatially associated with ABCA1-positive cells, including astrocytic profiles; perilipin 2 (PLIN2)-positive puncta were nearby. Pretreatment with the retinoid X receptor (RXR) agonist bexarotene increased hippocampal ABCA1 expression, delayed severe KA-induced behavioral seizure onset, and was associated with fewer chronic spontaneous seizures and reduced ectopic neuronal accumulation. Post-SE bexarotene administration was associated with lower seizure frequency, ectopic neuronal accumulation, and astrocytic marker-positive cell densities. Multi-omic profiling identified bexarotene-associated metabolic and lipidomic changes; transmission electron microscopy (TEM) showed a smaller mean hilar neuronal lipid-droplet area per image, and protein analyses identified early changes in p38 and extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Together, these findings warrant further investigation of astrocyte-associated lipid pathways as potential therapeutic targets in epilepsy-associated hippocampal remodeling.

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Cite

BibTeXRIS
BibTeX
@article{chen2026astrocyteassociated,
  title = {{Astrocyte-Associated ABCA1/APOE Responses Accompany Hippocampal Lipid Remodeling and Ectopic Neuronal Accumulation During Epileptogenesis.}},
  author = {Lu Chen and Xiao-Rui Shi and Jia-Yi Chen and Ying-Ting Wang and Le Du and Yang Ni and Jun-Min Chen and An-Chen Guo and Qian Wu and Jian-Ping Wu and Qun Wang},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78329},
  url = {https://europepmc.org/article/MED/42893447},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Astrocyte-Associated ABCA1/APOE Responses Accompany Hippocampal Lipid Remodeling and Ectopic Neuronal Accumulation During Epileptogenesis.
AU  - Lu Chen
AU  - Xiao-Rui Shi
AU  - Jia-Yi Chen
AU  - Ying-Ting Wang
AU  - Le Du
AU  - Yang Ni
AU  - Jun-Min Chen
AU  - An-Chen Guo
AU  - Qian Wu
AU  - Jian-Ping Wu
AU  - Qun Wang
PY  - 2026
DA  - 2026/10/18
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.78329
UR  - https://europepmc.org/article/MED/42893447
AB  - Temporal lobe epilepsy (TLE) is characterized by progressive hippocampal remodeling, including reactive astrogliosis and aberrant neuronal positioning. Although lipid disturbances are implicated in epileptogenesis, how astrocyte-associated lipid responses relate to hippocampal remodeling remains poorly understood. Here, human TLE and kainic acid (KA)-treated mouse transcriptomic datasets identified ATP-binding cassette transporter A1 (ABCA1)/Abca1 as a nominal astrocyte-associated candidate, while KA- and pilocarpine-induced status epilepticus (SE) elicited astrocyte-associated ABCA1/apolipoprotein E (APOE) responses. Ectopic granule cells and immature neurons accumulated in the hilus and were spatially associated with ABCA1-positive cells, including astrocytic profiles; perilipin 2 (PLIN2)-positive puncta were nearby. Pretreatment with the retinoid X receptor (RXR) agonist bexarotene increased hippocampal ABCA1 expression, delayed severe KA-induced behavioral seizure onset, and was associated with fewer chronic spontaneous seizures and reduced ectopic neuronal accumulation. Post-SE bexarotene administration was associated with lower seizure frequency, ectopic neuronal accumulation, and astrocytic marker-positive cell densities. Multi-omic profiling identified bexarotene-associated metabolic and lipidomic changes; transmission electron microscopy (TEM) showed a smaller mean hilar neuronal lipid-droplet area per image, and protein analyses identified early changes in p38 and extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Together, these findings warrant further investigation of astrocyte-associated lipid pathways as potential therapeutic targets in epilepsy-associated hippocampal remodeling.
SN  - 2198-3844
ER  -