Alteration of GABAergic signaling is associated with anxiety-like behavior in temporal lobe epilepsy mice

Abstract

Temporal lobe epilepsy (TLE), which is one of the most common neurological diseases, is accompanied by a high incidence of psychiatric disorders. Among these psychiatric disorders, anxiety is one of the major psychiatric comorbidities in epilepsy patients. However, anxiety in epilepsy patients often remains unrecognized and untreated. It is believed that the inhibitory networks of γ-aminobutyric acid (GABA) neurotransmission play pivotal roles in the modulation of emotion and mood responses in both physiological and pathological conditions. The impairment of neurotransmission mediated by GABAergic signaling is related to the pathophysiology of anxiety. However, it remains unclear whether and how GABAergic signaling modulates anxiety responses in the context of an epileptic brain. In the present study, we sought to determine the role of inhibitory networks of GABAergic signaling in the anxiety-like behavior of epileptic mice. Our results show epileptic mice exhibited increased anxiety-like behavior, and this increased anxiety-like behavior was accompanied by a decrease in GABAergic interneurons and an increase in GABA type A receptor (GABA_AR) β3 subunit (GABRB3) expression in the hippocampus. Furthermore, the activation of GABA_ARs produced an anxiolytic-like effect, while the inhibition of GABA_ARs elicited an anxiogenic-like effect in the epileptic mice, suggesting that the alteration of GABAergic signaling is associated with anxiety-like behavior in epileptic mice. Thus, targeting GABAergic signaling in the epileptic brain may provide an effective anxiolytic treatment in epilepsy patients.

Keywords: Anxiety; GABA; GABA(A)Rs; Hippocampus; Temporal lobe epilepsy.