Cannabinoid and vanilloid modulation of synaptic activity in the dentate gyrus of a mouse model of temporal lobe epilepsy
Description
Temporal lobe epilepsy (TLE) is a common neurological disorder that is characterized by changes in the neuronal circuitry that make the brain susceptible to seizure generation. Cannabinoid type 1 (CB1R) and vanilloid (TRPV1) receptors are widely distributed in the brain including the temporal lobe. Neurons are capable of making endogenous cannabinoids called endocannabinoids that can act on CB1R and TRPV1. Recent studies implicate a role for cannabinoids in the treatment of epilepsy. However, direct cellular effects of CB1R and TRPV1 activation in an epileptic brain that has undergone synaptic reorganization have been understudied. These experiments were aimed at studying the effects of CB1R and TRPV1 activation in the dentate gyms granule cells of a murine model of TLE that has undergone synaptic reorganization In mice with mossy fiber sprouting and spontaneous seizures following pilocarpine-induced status epilepticus, cannabinoid agonists suppressed excitatory synaptic activity. This effect was blocked by the selective CB1R antagonist, AM-251. In these mice, the TRPV1 agonist capsaicin increased excitatory synaptic activity and this increase was blocked by the selective TRPV1 antagonist capsazepine. Anandamide, an endocannabinoid, increased excitatory synaptic activity when CB1R were blocked with AM251 but suppressed the activity when TRPV1 were blocked with capsazepine. CB1R and TRPV1 protein levels were also increased in these animals. The data presented here support the hypothesis that there is an effective redistribution of CB1R and TRPV1 in the dentate gyms of epileptic mice and that activation of these receptors decrease and increase synaptic activity respectively. These studies elucidate the interaction between cannabinoid and vanilloid systems that is essential for the development of new therapeutic strategies for treating TLE based on the cannabinoid system