Open AccessHippocampal astrocytic neogenin regulating glutamate uptake, a critical pathway for preventing epileptic response
Author(s) -
Dong Sun,
Zhibing Tan,
Xiangdong Sun,
Zhipeng Liu,
WenBing Chen,
Leena Milibari,
Xiao Ren,
Lingling Yao,
Daehoon Lee,
Chen Shen,
Jin-Xiu Pan,
Zhihui Huang,
Lin Mei,
WenCheng Xiong
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022921118
Subject(s) - biology , hippocampal formation , inhibitory postsynaptic potential , microbiology and biotechnology , astrocyte , neuroscience , excitatory postsynaptic potential , glutamate receptor , neurotransmission , gabaergic , central nervous system , receptor , biochemistry
Significance Epilepsy, a neurological disorder, is caused by abnormal brain activity due to genetic variances or acquired brain injuries. However, the underlying molecular mechanisms remain elusive. We demonstrate that NEO1, a member of the deleted in colorectal cancer (DCC) family transmembrane proteins, is decreased in human hippocampi of patients with epilepsy. By using a combination of genetic, electrophysiological, biochemical, and molecular biological methods, we show that KONeo1 in hippocampal astrocytes, but not in neurons, increased epileptiform spikes and seizure susceptibility in mice. Astrocyte-specific KO ofNeo1 reduced inhibitory synaptic vesicles and GABAergic synaptic transmission in the hippocampus by impairing the GLAST-mediated glutamate–glutamine cycle. Together, this study reveals a function of NEO1 in hippocampal astrocytes to protect the brain from epilepsy.