Nitric oxide-containing neurons in long-term grafts in a rat model of Parkinson's disease.
The role that nitric oxide may play in modulating graft function in long-term fetal ventral mesencephalic grafts in an animal model of Parkinson's disease was investigated. Mature grafts harvested from the entire fetal ventral mesencephalon possessed a large number of neuronal nitric oxide synthase (nNOS)/NADPH-diaphorase-containing neurons throughout the graft intermingled with dopaminergic neurons. The morphological and neurochemical characteristics of these NADPH-diaphorase neurons resembled those in centers adjacent to the substantia nigra of adult brain but not that of the striatum. Pretreatment with the nNOS blocker, 7-nitroindazole, resulted in contralateral rotations following methamphetamine challenge in long-term grafted animals that previously showed normalized rotational behavior. In contrast, mature grafts derived from fetal ventral mesencephalon without the midline areas possessed only a few nNOS-containing neurons within the grafts, and a similar methamphetamine challenge following 7-nitroindazole pretreatment in long-term grafted rats that previously showed normalized rotational behavior resulted in random movements. Our results indicate that nitric oxide-containing neurons inadvertently included during grafting may affect graft function, and excluding the midline areas of the ventral mesencephalon during tissue harvesting may minimize this effect.
Rajakumar
B
B
Department of Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada.
Flumerfelt
B A
BA
Hrycyshyn
A W
AW
Rajakumar
N
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D010300:Parkinson Disease / Q000473:pathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013004:Somatostatin / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D007191:Indazoles; D009569:Nitric Oxide; D008694:Methamphetamine; D013004:Somatostatin; D014446:Tyrosine 3-Monooxygenase; D009252:NADPH Dehydrogenase; D002794:Choline; C080122:7-nitroindazole