Details

Autor(en) / Beteiligte

• Fu, Min
• Xie, Zuoping
• Zuo, Huancong

Titel

TRPV1: A potential target for antiepileptogenesis

Ist Teil von

• Medical hypotheses, 2009-07, Vol.73 (1), p.100-102

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Epilepsy is one of the most common diseases in neurology department. It is caused by many different kinds of perturbances of normal balance of excitation and inhibition within the central nervous system. Current clinical antiepileptic drugs (AEDs) targets include ion channels, neurotransmitter transporters and neurotransmitter metabolic enzymes. They could control about 70–80% of the patients’ symptoms; 20–30% patients develop to be intractable epilepsy sufferers. Moreover, antiepileptic drugs could not prevent formation of foci and disease process, but only alleviate symptoms of seizures at risk of different adverse effects as the consequences of large doses. Recently, impressive data on the actions of transient receptor potential vanilloid receptor 1 (TRPV1) prove it to be an inspiring antiepileptogenic target. TRPV1 activation modulates activity-dependent synaptic efficacy: (i) facilitating long-term potentiation (LTP) and suppressing long-term depression (LTD) of hippocampal neurons (ii) selectively inhibiting excitatory synapses onto hippocampal interneurons, which is expected to increase the excitability of innervated pyramidal cells. Nerve growth factor (NGF) can acutely and chronically upregulates TRPV1 expression, suggesting that TRPV1 channels would play an important role in the course of NGF regulated epileptogenesis. Endocannabinoid anandamide (AEA) is one of the TRPV1 endogenous agonists. It has been proved that, in the course of epilepsy, AEA levels increases due to enhanced formation and both exogenously administered and endogenously produced AEA display proconvulsant activity. Moreover, TRPV1 activation triggers apoptotic neuronal death of rat cortical cultures, which may be responsible, at least in part, for the volume loss of neocortex in chronic epilepsy. Our hypothesis may broaden the drug screening and designing for clinical strategies for epilepsy treatment.