Increased expression of DOC2A in human and rat temporal lobe epilepsy

Abstract

Temporal lobe epilepsy (TLE) is the most common form of intractable epilepsy. Currently, the molecular mechanisms underlying epileptogenesis in TLE remain elusive; however, synaptic transmission may play an important role in the pathogenesis of epilepsy. Synaptic transmission is regulated by diverse mechanisms, including presynaptic modulators of synaptic vesicle formation and release, modulators of neurotransmission and distinct Ca2+ sensors. DOC2A, a novel Ca2+ sensor, can regulate spontaneous synaptic transmission and has been implicated in Ca2+-dependent neurotransmitter release. In this study, we demonstrate for the first time that DOC2A expression is significantly increased in human TLE and in two different rat models of TLE (pilocarpine- and kindling-induced) compared to the control groups. Localization of DOC2A in the human TLE patients and pilocarpine post-SE rat model was observed in neurons but not in astrocytes; DOC2A was also concentrated at the presynaptic terminals and colocalized with VMAT2. Our results suggest that the abnormal protein expression of DOC2A in epileptic brain tissue may play an important role in epilepsy.