Participation of the dentate‐rubral pathway in the kindling model of epilepsy

Abstract

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. GAD , a GABA-synthesizing enzyme, was increased in kindled rats and decreased after DN lesions. GAD 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 GAD 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 GAD 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.

Brain iron assessment in patients with First-episode schizophrenia using quantitative susceptibility mapping

“…In addition, Kirsten et al repeatedly reported increased glutamate in the left thalamus of schizophrenia patients ( Kirsten et al, 2018 , Kirsten et al, 2017 ). The RN is known to contain measurable amounts of glutamatergic and GABAergic neurons and receives the glutamatergic fibers from dentate nucleus of the cerebellum ( Hernandez-Ceron et al, 2017 , Nieoullon et al, 1988 ). The hypoactive GABAergic interneurons and hyperactive glutamate neurons have been demonstrated in the cerebellar cortices of patients with schizophrenia ( Bullock et al, 2008 , Paz et al, 2006 ).…”

Effects of Lateral Cerebellar Nucleus Stimulation on Seizures in Rats Kindled to Different Levels of Seizure Severity with PTZ

“…Contradictory data on the role of cerebellar structures, including LCN destruction as a recommended therapeutic approach in epileptic patients [10,41], might be reconsidered from the delivered signi cance of LCN for the maintenance of myoclonic seizure manifestations.…”

“…Brain stimulation may be an alternative approach to resistant epilepsy control [6,7]. Stimulation of cerebellar structures such as the nuclei and cortex has been investigated for their induction of antiepileptic effects [8][9][10][11]. Earlier suppression of penicillin-induced cortical foci with contralateral nucleus dentatus (lateral cerebellar nucleus (LCN) electrical stimulation (ES)) was shown in cats [12].…”