RT Journal Article
SR Electronic
T1 The PDGFBB-PDGFRβ Pathway and Laminins in Pericytes Are Involved in the Temporal Change of AQP4 Polarity during Temporal Lobe Epilepsy Pathogenesis
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0196-25.2025
DO 10.1523/ENEURO.0196-25.2025
VO 12
IS 10
A1 Lin, Lin
A1 Tang, Hongxia
A1 Cui, Ke
A1 Kang, Zeyi
A1 Pan, Tengwei
A1 Feng, Changqiang
A1 Zhao, Xiaohong
A1 Wang, Jiewei
A1 Chen, Zhiyuan
A1 Jiang, Zhengli
A1 Wu, Gang
YR 2025
UL http://www.eneuro.org/content/12/10/ENEURO.0196-25.2025.abstract
AB This study aims to examine the changes in AQP4 polarity and pericyte vascularity during temporal lobe epilepsy (TLE) progression, with the goal of identifying potential drug targets or strategies to delay the onset and progression of TLE. Chronic TLE was induced in male rats using pilocarpine. AQP4 polarity and pericyte vascular coverage were assessed by immunofluorescence. The effects of modulating AQP4 polarity on PTZ-induced TLE model using male mice were studied. Molecular mechanisms of AQP4 polarity were explored using transwell coculture and transcriptomics, validated at the protein level. ELISA was used to measure PDGF-BB levels in serum and cerebrospinal fluid. Following pilocarpine-induced chronic TLE model establishment, AQP4 polarity and pericyte vascular coverage rapidly increased but later declined, reaching the lowest levels in epileptic animals. Trifluoperazine prevented AQP4 redistribution, reduced seizure duration, and alleviated brain edema in PTZ-induced TLE mouse model. Transcriptomic analysis revealed that pericyte coculture did not alter the expression of dystrophin-associated protein components in astrocytes. Pericyte LAMA1 and LAMA2 levels were significantly higher than endothelial cells, and the levels of pericyte LAMA1 and LAMA2 were significantly increased after coculture with astrocytes. Expression of LAMA1 and LAMA2 around pericytes initially increased and then decreased during chronic TLE progression. PDGF-BB levels decreased over time, reaching the lowest levels during epilepsy. Disrupted AQP4 polarity is closely associated with TLE development. Pericyte vascular coverage appears to influence AQP4 polarity, and key molecules such as laminins and PDGF-BB may help maintain AQP4 polarity, potentially contributing to the attenuation of TLE progression and epileptogenesis.