Nitric oxide-containing neurons in long-term grafts in a rat model of Parkinson's disease

• Published in: Cell transplantation Vol. 16; no. 5; p. 449
• Main Authors: Rajakumar, B, Flumerfelt, B A, Hrycyshyn, A W, Rajakumar, N
• Format: Journal Article
• Language: English
• Published: United States SAGE Publishing 01-01-2007
• Subjects: Animals; Behavior, Animal - drug effects; Brain Tissue Transplantation; Choline - metabolism; Disease Models, Animal; Female; Indazoles - pharmacology; Methamphetamine - pharmacology; NADPH Dehydrogenase - metabolism; Neostriatum - drug effects; Neurons - drug effects; Neurons - enzymology; Neurons - metabolism; Neurons - pathology; Nitric Oxide - metabolism; Parkinson Disease - pathology; Pedunculopontine Tegmental Nucleus - drug effects; Pedunculopontine Tegmental Nucleus - metabolism; Pedunculopontine Tegmental Nucleus - pathology; Pregnancy; Rats; Rats, Sprague-Dawley; Rotation; Somatostatin - metabolism; Time Factors; Tyrosine 3-Monooxygenase - metabolism; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - pathology
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/000000007783464975

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.