Endogenous modulators of hyperexcitability in epilepsy: electrophysiological and optogenetic delineation of neuropeptide Y mechanisms in interneurons
type: CreativeWork
description: Epilepsy is one of the most common neurological disorders worldwide, affecting 1% of the general population, and is characterized by a predisposition for the generation of epileptic seizures. Despite having several different aetiologies, a common underlying cause of epilepsy seems to be an acquired imbalance between excitatory and inhibitory circuits in the brain, which leads to hyperexcitability and appearance of seizures. Current treatment relies on the use of antiepileptic drugs (AEDs), but these only treat the symptoms, not affect the causes of the disease, and trigger undesirable side effects because of their systemic administration. Recent advancements in drug discovery have led to the development of new AEDs that are better tolerated and with improved pharmacokinetics, but 30-40% of all patients with epilepsy, and particularly those with temporal lobe epilepsy (TLE) remain resistant to the treatment. Thus, there is an urgent need for developing new antiepileptic treatment strategies. In the last years, research on novel antiepileptic treatments has identified several endogenous molecules as potential new targets for therapeutic intervention. Among these, neuropeptide Y (NPY ) seems to be a particularly promising target, as it plays an important role in controlling neuronal excitability in different brain areas, including the hippocampus. Indeed, overexpression of NPY via gene therapy approaches in animal models of epilepsy has profound effects on seizure generation and suppression, providing proof of principle evidence that such approach could be successfully used to reduce and control seizures. The actions of NPY are mediated by various receptors, and their activation predominantly causes suppression of glutamatergic synaptic transmission, which leads to decreased excitability. However, little is known about the effect NPY has on GABAergic inhibitory cell populations, and NPY mechanisms of action have to be carefully determined if such an approach could be u…
abstract: Epilepsy is one of the most common neurological disorders worldwide, affecting 1% of the general population, and is characterized by a predisposition for the generation of epileptic seizures. Despite having several different aetiologies, a common underlying cause of epilepsy seems to be an acquired imbalance between excitatory and inhibitory circuits in the brain, which leads to hyperexcitability and appearance of seizures. Current treatment relies on the use of antiepileptic drugs (AEDs), but these only treat the symptoms, not affect the causes of the disease, and trigger undesirable side effects because of their systemic administration. Recent advancements in drug discovery have led to the development of new AEDs that are better tolerated and with improved pharmacokinetics, but 30-40% of all patients with epilepsy, and particularly those with temporal lobe epilepsy (TLE) remain resistant to the treatment. Thus, there is an urgent need for developing new antiepileptic treatment strategies. In the last years, research on novel antiepileptic treatments has identified several endogenous molecules as potential new targets for therapeutic intervention. Among these, neuropeptide Y (NPY ) seems to be a particularly promising target, as it plays an important role in controlling neuronal excitability in different brain areas, including the hippocampus. Indeed, overexpression of NPY via gene therapy approaches in animal models of epilepsy has profound effects on seizure generation and suppression, providing proof of principle evidence that such approach could be successfully used to reduce and control seizures. The actions of NPY are mediated by various receptors, and their activation predominantly causes suppression of glutamatergic synaptic transmission, which leads to decreased excitability. However, little is known about the effect NPY has on GABAergic inhibitory cell populations, and NPY mechanisms of action have to be carefully determined if such an approach could be u…
author: Ledri, Marco
language: eng
keywords: Neurology, interneurons, Epilepsy, Neuropeptide Y, synaptic transmission, synaptic plasticity, electrophysiology, optogenetics
date published: 2012
date modified: 2026-07-24T02:59:49Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Experimental Epilepsy Group, Division of Neurology, Department of Clinical Sciences.