Aller au contenuAller au menuAller à la recherche

João O. Malva "Neuroprotective and antieplileptogenic role of NPY receptors in kainate-induced excitotoxicity and epilepsy"

Abstract :


K
ainate-induced epilepsy has been shown to be associated with increased levels of neuropeptide Y (NPY) in the rat hippocampus. However, the functional role of NPY in controlling neuronal function in epilepsy and neuroprotection is not well understood.
Presynaptic NPY receptors (Y2 subtype) have been shown to play a key role in the presynaptic modulation of glutamate release, in the hippocampus. By decreasing presynaptic excitability it is reasonable to expect that the activation of NPY Y2 receptors may trigger putative neuroprotective mechanisms against excitotoxic insults.
We show that in the acute phase of kainate-induced epilepsy, in rats, the transient loss of NPY Y2 receptor-mediated inhibition of glutamate release can contribute to increase hyperexcitability of the hippocampal tissue and account for the generation of seizures. Moreover, in the chronic phase of kainate-induced epilepsy the increased expression of NPY and increased levels of Y2 receptors may act together to control neuronal hyperexcitability by triggering a tonic-like inhibition of glutamate release by involving increased NPY release and activation of NPY Y2 receptors.
The excitotoxic insults that may occur in parallel with seizure activity may be responsible for excitotoxic cell death. By using organotypic cultures of rat and mouse hippocampal slices we could show that the activation of NPY Y2 receptors can prevent, and rescue, neurons from dying after the occurrence of excitotoxic insults.
The role of NPY as a potential endogenous antiepileptic and neuroprotective presynaptic modulator is now being revealed. The better understanding of the role of NPY in epilepsy and the intracellular interaction with survival pathways may contribute, at the long-term, to development of new drug-based therapeutic strategies for chemo-resistant forms of human temporal lobe epilepsy.

Christophe Mulle