Adrenal medullary cells transmute into dopaminergic neurons in dopamine-depleted rat caudate and ameliorate motor disturbances.
Adrenal medullary cell suspensions, derived from newborn rats (postnatal day 1-6), were implanted into the head of the caudate nucleus in 35 rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopamine (DA) pathway. Behavioral recovery from Met-amphetamine induced circling, cell growth and morphological features (tyrosine hydroxylase positive cells), and release of adrenaline (Ad), noradrenaline (NA), DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated for 40 weeks after transplantation. Met-amphetamine induced circling decreased significantly in 43% (15/35) of the rats. The decrease was concurrent with transmutation of the tyrosine hydroxylase-like immunopositive (THLI) cells into mature neurons that had abundant elongated neurites with varicosities and synapses on neuronal elements in the host caudate. In the absence of behavioral recovery (57%, 20/35) THLI cells were very scant. DA, DOPAC and HVA were reduced more than 90% in perfusates collected by in vivo dialysis from the striata of the animals that were not improved by transplant. These levels recovered to 20-50% of controls in animals whose behavior recovered. Ad and NA were not detected in the perfusates of either recovered or non-recovered animals. The results suggest that some grafted adrenal medullary cells transform into dopaminergic neurons and the release of DA from these grafted cells functionally affects behavior improvement for at least 40 weeks.
D000313:Adrenal Medulla / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000648:ultrastructure; D002421:Caudate Nucleus / Q000502:physiology* / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006651:Histocytochemistry; D006892:Hydroxydopamines; D008694:Methamphetamine / Q000494:pharmacology; D008854:Microscopy, Electron; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D016627:Oxidopamine; D051381:Rats; D013569:Synapses / Q000201:enzymology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D006892:Hydroxydopamines; D008694:Methamphetamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine