Inhibition of granule cell dispersion and seizure development by AAV1-AEG-1 administration in a mouse model of TLE

Abstract Although granule cell dispersion (GCD) in the hippocampus is known to be an important feature associated with epileptic seizures in temporal lobe epilepsy (TLE), the endogenous molecules that regulate GCD remain elusive. Here, we have identified that the expression of astrocyte elevated gene-1 (AEG-1) is upregulated in the dentate gyrus (DG) of a kainic acid (KA)-induced mouse model of TLE. We further demonstrated that AEG-1 upregulation by adeno-associated virus 1 (AAV1) delivery in the DG induced anticonvulsant activities such as the delay of seizure onset and inhibition of spontaneous recurrent seizures (SRS) through GCD suppression in the mouse model of TLE, while the inhibition of AEG-1 expression increased susceptibility to seizures. Thus, the present observations suggest that AEG-1 is a novel regulator of GCD formation and seizure development associated with TLE, and the induction of AEG-1 in the DG may have therapeutic potential against epilepsy.