Galanin type 2 receptors regulate neuronal survival, susceptibility to seizures and seizure-induced neurogenesis in the dentate gyrus.
The neuropeptide galanin has been implicated in inhibiting seizures and protecting hippocampal neurons from excitotoxic injury. In the hippocampus galanin acts through two receptor subtypes, GalR1, expressed in CA1, and GalR2, abundant in dentate gyrus. We developed an approach to induce and to study selective semichronic knockdown of GalR2 in the rat hippocampus. A 50% reduction of GalR2 binding was achieved by continuous infusion of complementary peptide nucleic acid antisense oligonucleotide into the dentate gyrus. This resulted in an increase in the severity of self-sustaining status epilepticus induced by electrical stimulation of the perforant path, induced mild neuronal injury in the dentate hilus, augmented seizure-induced hilar injury and inhibited seizure-induced neurogenesis in the subgranular zone of the dentate gyrus. Our data suggest that in the dentate gyrus, galanin, acting through GalR2, inhibits seizures, promotes viability of hilar interneurons and stimulates seizure-induced neurogenesis. These results are important for understanding the role of galanin and galanin receptor subtypes in the hippocampus both under normal conditions and in excitotoxic injury.
Mazarati
Andrey
A
West Los Angeles VA Medical Center, and Department of Neurology, D. Geffen Medical School, UCLA, Los Angeles, CA, USA. mazarati@ucla.edu
Lu
Xiaoying
X
Kilk
Kalle
K
Langel
Ulo
U
Wasterlain
Claude
C
Bartfai
Tamas
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation; D004558:Electric Stimulation; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D044092:Receptor, Galanin, Type 2 / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*; D013226:Status Epilepticus / Q000150:complications / Q000503:physiopathology
D000927:Anticonvulsants; D016376:Oligonucleotides, Antisense; D044092:Receptor, Galanin, Type 2; D019004:Galanin