Intranigral transplants of a GABAergic cell line produce long-term alleviation of established motor seizures.
We have previously shown that intranigral transplants of immortalized GABAergic cells decrease the number of kainic acid-induced seizures [Castillo CG, Mendoza S, Freed WJ, Giordano M. Intranigral transplants of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat. Behav Brain Res 2006;171:109-15] in an animal model. In the present study, recurrent spontaneous behavioral seizures were established by repeated systemic injections of this excitotoxin into male Sprague-Dawley rats. After the seizures had been established, cells were transplanted into the substantia nigra. Animals with transplants of control cells (without hGAD67 expression) or with sham transplants showed a death rate of more than 40% over the 12 weeks of observation, whereas in animals with M213-2O CL-4 transplants, the death rate was reduced to less than 20%. The M213-2O CL-4 transplants significantly reduced the percentage of animals showing behavioral seizures; animals with these transplants also showed a lower occurrence of stage V seizures than animals in the other groups. In vivo and in vitro analyses provided evidence that the GABAergic cells show sustained expression of both GAD67 and hGAD67 cDNA, as well as increased gamma-aminobutyric acid (GABA) levels in the ventral mesencephalon of transplanted animals. Therefore, transplantation of GABA-producing cells can produce long-term alleviation of behavioral seizures in an animal model.
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico. cgcastillo@cbm.uam.es
Claudia G
CG
Castillo
Soledad
S
Mendoza-Trejo
Manuel B
MB
Aguilar
William J
WJ
Freed
Magda
M
Giordano
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006690:Bisbenzimidazole / Q000378:metabolism; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D019084:Fluorescent Antibody Technique, Indirect; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000601:surgery*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000096:biosynthesis* / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D006690:Bisbenzimidazole; D007608:Kainic Acid