Hippocampal astrocytic neogenin regulating glutamate uptake, a critical pathway for preventing epileptic response.

ABSTRACT: Epilepsy, a common neurological disorder, is featured with recurrent seizures. Its underlying pathological mechanisms remain elusive. Here, we provide evidence for loss of neogenin (NEO1), a coreceptor for multiple ligands, including netrins and bone morphological proteins, in the development of epilepsy. NEO1 is reduced in hippocampi from patients with epilepsy based on transcriptome and proteomic analyses. Neo1 knocking out (KO) in mouse brains displays elevated epileptiform spikes and seizure susceptibility. These phenotypes were undetectable in mice, with selectively depleted NEO1 in excitatory (NeuroD6-Cre⁺) or inhibitory (parvalbumin⁺) neurons, but present in mice with specific hippocampal astrocytic Neo1 KO. Additionally, neurons in hippocampal de

SUBMITTER: Sun D 

PROVIDER: S-EPMC8072226 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature