title: Embryonic stem cells derived neuron transplantation recovery in models of parkinsonism in relation to severity of the disorder in rats.
abstract: 6-Hydroxydopamine (6-OHDA)- and 1-methyl-4-phenylpyridinium (MPP(+))-induced hemi-parkinsonism was investigated in relation to the severity of the disorder in terms of behavioral disability and nigral neuronal loss and recovery regarding the number of stem cell-derived neurons transplanted in the striatum. Intra-median forebrain bundle infusion of the parkinsonian neurotoxins and intra-striatal transplantation of differentiated embryonic stem cells (ESCs) were carried out by rat brain stereotaxic surgery. The severity of the disease was determined using the number of amphetamine- or apomorphine-induced rotations, striatal dopamine levels as estimated by high-performance liquid chromatography (HPLC)-electrochemistry, and the number of surviving tyrosine hydroxylase immunoreactive dopaminergic neurons in the substantia nigra pars compacta. Rats that received unilateral infusion of 6-OHDA or MPP(+) responded with dose-dependent, unilateral bias in turning behavior when amphetamine or apomorphine was administered. Rotational asymmetry in both models correlated significantly well with the loss in the number of nigral dopaminergic neurons and striatal dopamine depletion. Transplantation of 2×10(5) differentiated murine ESCs revealed remarkably similar kinds of recovery in both animal models. The survival of the grafted dopaminergic cells in the striatum was better in animals with low-severity parkinsonism, but poor in the animals with severe parkinsonism. Amphetamine-induced rotational recovery correlated positively with an increasing number of cells transplanted in animals with uniform nigral neuronal lesion. These results suggest that disease severity is an important factor for determining the number of cells to be transplanted in parkinsonian rats for desirable recovery, which may be true in clinical conditions too.
authors.affiliation: 1 Division of Cell Biology & Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology , Jadavpur, Kolkata, India .
authors.forename: Reena
authors.initials: R
authors.lastname: Haobam
authors.forename: Debasmita
authors.initials: D
authors.lastname: Tripathy
authors.forename: Navneet A
authors.initials: NA
authors.lastname: Kaidery
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001479:Basal Ganglia / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000637:transplantation*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000637:transplantation*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D065842:Pars Compacta / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine