Possible exploitation of non-neuronal and non-chemical synaptic signalling pathways in epilepsy therapy

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Abstract

Although approximately 1% of the human population suffers from epilepsy, the cellular basis of this disease remains largely unresolved and about 30% of all epilepsies are refractory to therapies using currently available drugs. Until recently, synchronous neuronal activity during seizures has been thought to be, entirely of neuronal origin, and the main stream of epilepsy research has focused on changes in membrane properties of neurons and on classical chemical neurotransmission between them. However, recent discoveries about neuron-astrocyte bidirectional communication strongly challenge this concept. These functions of astrocyte are proving significant in the understanding of epilepsy, stroke and many other neurological diseases. In addition, the most important function reported for gap junctional communication in the nervous system is the increased synchronous activity of the coupled cells. Based on the emergent evidence, it is likely that gap junctional communication plays a definite role in the associated neuronal/ astrocytic networks being involved in the generation and propagation of seizure discharges in the epileptic brain. Therefore astrocytes and gap junctions as potentially new cellular targets may open new perspectives for targeted molecular therapeutic interventions and allow the development of new antiepileptic as well as anticonvulsant drugs.

Original languageEnglish
Pages (from-to)215-230
Number of pages16
JournalCurrent Signal Transduction Therapy
Volume3
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Epilepsy
Astrocytes
Communication
Anticonvulsants
Seizures
Neurons
Gap Junctions
Therapeutics
Synaptic Transmission
Nervous System
Stroke
Membranes
Brain
Research
Pharmaceutical Preparations
Population

Keywords

  • Anticonvulsant drugs
  • Antiepileptic drugs
  • Astrocytes
  • Epilepsy
  • Gap junctions

ASJC Scopus subject areas

  • Endocrinology
  • Pharmacology (medical)

Cite this

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abstract = "Although approximately 1{\%} of the human population suffers from epilepsy, the cellular basis of this disease remains largely unresolved and about 30{\%} of all epilepsies are refractory to therapies using currently available drugs. Until recently, synchronous neuronal activity during seizures has been thought to be, entirely of neuronal origin, and the main stream of epilepsy research has focused on changes in membrane properties of neurons and on classical chemical neurotransmission between them. However, recent discoveries about neuron-astrocyte bidirectional communication strongly challenge this concept. These functions of astrocyte are proving significant in the understanding of epilepsy, stroke and many other neurological diseases. In addition, the most important function reported for gap junctional communication in the nervous system is the increased synchronous activity of the coupled cells. Based on the emergent evidence, it is likely that gap junctional communication plays a definite role in the associated neuronal/ astrocytic networks being involved in the generation and propagation of seizure discharges in the epileptic brain. Therefore astrocytes and gap junctions as potentially new cellular targets may open new perspectives for targeted molecular therapeutic interventions and allow the development of new antiepileptic as well as anticonvulsant drugs.",
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