Galanin and epilepsy.
Neuroanatomical localization and physiological properties of galanin suggest that the peptide may be involved in the regulation of seizures. Indeed, administration of galanin receptor agonists into brain areas pertinent to the initiation and propagation of epileptic activity attenuated seizure responses under conditions of animal models of epilepsy; pharmacological blocking of galanin receptors exerted proconvulsant effects. Functional deletion of both galanin and galanin type 1 receptor genes produced transgenic mice with either spontaneous seizure phenotype, or with enhanced susceptibility to seizure stimuli. At the same time, overexpression of galanin in seizure pathways, using both transgenic and virus vector transfection techniques, hindered the epileptic process. Galanin exerts anticonvulsant effects through both type 1 and type 2 receptors, with distinct downstream signaling cascades. Several synthetic agonists of galanin receptors with optimized bioavailability have been synthesized and inhibited experimental seizures upon systemic administration, thus opening an opportunity for the development of galanin-based antiepileptic drugs.
Lerner
J T
JT
Dept. of Pediatrics, Neurology Division, D. Geffen School of Medicine at the University of California, Los Angeles, BOX 951752, 22-474 MDCC, Los Angeles, California 90095-1752, USA.
Sankar
R
R
Mazarati
A M
AM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000209:etiology; D019004:Galanin / Q000494:pharmacology / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D051381:Rats; D044088:Receptors, Galanin / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction
D000927:Anticonvulsants; D044088:Receptors, Galanin; D019004:Galanin