The endocannabinoid system plays a central role in retrograde
synaptic communication, and controls both glutamatergic and
gamma-aminobutyric acid (GABA)ergic transmission via type 1
cannabinoid (CB1) receptor. Both in sclerotic human hippocampi
and in the chronic phase of pilocarpine-induced epilepsy in mice
with sclerosis, CB1-receptor-positive interneuron somata were
preserved both in the dentate gyrus and in the CA1 area, and the
density of CB1-immunostained fibers increased considerably in
the dentate molecular layer. This suggests that, although CB1
receptors are known to be reduced in density on glutamatergic
axons, the CB1-receptor-expressing GABAergic axons sprout, or
there is an increase of CB1-receptor levels on these fibers. The
changes of CB1 immunostaining in association with the GABAergic
inhibitory system appear to correlate with the severity of
pyramidal cell loss in the CA1 subfield. These results confirm
the involvement of the endocannabinoid system associated with
GABAergic transmission in human temporal lobe epilepsy (TLE),
as well as in the chronic phase of the pilocarpine model in
mice. Pharmacotherapy aimed at the modulation of
endocannabinoid-mediated retrograde synaptic signaling should
take into account the opposite change in CB1-receptor expression
observed on glutamatergic versus GABAergic axon terminals.
