Participation of the dentate-rubral pathway in the kindling model of epilepsy.

Lesions of the cerebellar dentate nucleus (DN) reduce the after-discharge duration induced by repetitive kindling stimulation and decrease seizures to a lower rank according to Racine's scale. The DN sends cholinergic and glutamatergic fibers to the red nucleus (RN), which is composed of glutamatergic and GABAergic cells. To test the participation of these neurotransmitters in seizures, we compared the levels of glutamate and gamma-aminobutyric acid (GABA) at the RN in a control condition, a kindled stage, and a kindled stage followed by DN lesions. We found that the kindled stage was associated with significant reductions in glutamate and GABA in the RN and that the lesions of the DN in kindled rats reversed the severity of seizures and restored the GABA levels. GAD65 , a GABA-synthesizing enzyme, was increased in kindled rats and decreased after DN lesions. GAD65 commonly appears localized at nerve terminals and synapses, and it is only activated when GABA neurotransmission occurs. Thus, it is possible that the increased expression of GAD65 found in kindled rats could be due to an exacerbated demand for GABA due to kindled seizures. It is known that GABA maintains the inhibitory tone that counterbalances neuronal excitation. The decreased expression of GAD65 found after the DN lesions indicated that the GABA-synthesizing enzyme was no longer required once it eliminated the excitatory glutamate input to the RN. We thus conclude that DN lesions and their consequent biochemical changes are capable of decreasing the generalized seizures induced by kindling stimulation. © 2016 Wiley Periodicals, Inc.