Recombinant AAV-mediated expression of galanin in rat hippocampus suppresses seizure development.
Galanin, a 29- or 30-amino acid neuropeptide, has been implicated in the modulation of seizures. In this study, we constructed a recombinant adeno-associated viral (AAV) vector to constitutively over-express galanin (AAV-GAL). The vector mediated efficient transduction of HEK 293 cells in vitro and robust galanin expression in vivo when injected into the rat dorsal hippocampus. Rats were administered kainic acid intrahippocampally 2.5 months following AAV-GAL or empty vector (AAV-Empty) injection to study the effect of vector-mediated galanin over-expression on seizures. AAV-GAL-injected rats showed a decreased number of seizure episodes and total time spent in seizures compared to AAV-Empty rats, despite similar latencies to development of the first EEG seizure and similar levels of neuronal damage in the CA3 region for both groups. These data show that recombinant AAV mediates strong and stable over-expression of galanin when injected into the rat hippocampus resulting in a significant anticonvulsive effect. The seizure suppression effect of galanin expression in the hippocampus by viral vectors may lead to novel therapeutic strategies for the treatment and management of intractable seizures with focal onset such as temporal lobe epilepsy.
Lin
En-Ju D
EJ
Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
Richichi
Cristina
C
Young
Deborah
D
Baer
Kristin
K
Vezzani
Annamaria
A
During
Matthew J
MJ
D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D007839:Functional Laterality; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D007668:Kidney; D008297:Male; D009930:Organic Chemicals; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; D019004:Galanin; D007608:Kainic Acid