AJAP1 affects behavioral changes and GABABR1 level in epileptic mice

• Published in: Biochemical and biophysical research communications 2020-04, Vol.524 (4), p.1057-1063
• Main Authors: Zhang, Mingli, Zhou, Xueying, Jiang, Wei, Li, Min, Zhou, Ruijiao, Zhou, Shengnian
• Format: Article
• Language: English
• Subjects: AJAP1; Epilepsy; GABABR1; Lentivirus; Therapeutic target
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.02.036

Adherens junction-associated protein-1 (AJAP1), also called SHREW1, was first discovered as a novel component of adherens junctions in 2004. In later studies, AJAP1 was found to suppress invasion and predict recurrence of some tumors. Apart from its function as a putative tumor suppressor, AJAP1 is still poorly understood. Schwenk et al. recently found that AJAP1 was tightly associated with the γ-Aminobutyric acid type B receptor subunit 1(GABABR1). It is well known that GABABR plays a vital role in epilepsy as an inhibitory transmitter receptor. Structurally adjacent, possibly functionally interacting, therefore, we hypothesize that AJAP1 participates in the onset and progression of epilepsy. We designed this experiment to investigate the expression and location of AJAP1 in temporal lobe epilepsy (TLE) patients and kainic acid(KA)-induced epilepsy animal models by immunofluorescence and Western blot analyses. We overexpressed and inhibited AJAP1 through lentiviruses in KA-induced models and observed the corresponding effects on epileptic animals. Double-label immunofluorescence showed that AJAP1 was expressed mainly in neurons. Western blot analysis revealed that AJAP1 expression was downregulated in the neocortex of TLE patients and the hippocampus and neocortex of epileptic animal models. The overexpression of AJAP1 can reduce the frequency of spontaneous seizures, whereas the inhibition of AJAP1 expression can increase the incidence rate. Our study demonstrated that AJAP1 may be involved in the pathogenic process of epilepsy and may represent a novel antiepileptic target. •Our study confirms that AJAP1 is closely related to epilepsy.•The expression of AJAP1 decreased in epileptic patients and animal models.•We have recorded the behavioral changes in epileptic mice with different levels of AJAP1.•We found that epilepsy was negatively correlated with the level of AJAP1.•In epileptic mice, different expression of AJAP1 affects the levels of GABABR1.