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Pattern of long‐term sensorimotor recovery following intrastriatal and ‐accumbens DA micrografts in a rat model of Parkinson's disease
Author(s) -
Falkenstein Gero,
Rosenthal Christoph,
Reum Torsten,
Morgenstern Rudolf,
Döbrössy Máté,
Nikkhah Guido
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22035
Subject(s) - forelimb , putamen , nucleus accumbens , dopaminergic , neuroscience , biology , transplantation , caudate nucleus , parkinson's disease , dopamine , pathology , medicine , disease
The functional restorative capacity of fetal dopaminergic (DA) transplants is governed by a number of critical parameters including graft location, survival of DA neurons, and transplantation technique. In addition, there is an ongoing controversy whether “too much” or “too little” survival of DA neurons is responsible for the incomplete functional recovery observed in some transplanted Parkinson's disease (PD) patients. Here we investigated two implantation sites, the nucleus accumbens (NAc) and the caudate‐putamen unit (CPU), and two different graft distributions within the CPU, i.e., two 0.75 μL deposits (CPU‐2) versus six 0.25 μL deposits (CPU‐6) in a rat model of PD. Grafts were derived from E14 rat ventral mesencephalon and the long‐term functional outcome was evaluated with a wide range of complex‐sensorimotor behavioral tests. The data show that forelimb stepping, balancing behavior, and skilled forelimb reaching behavior was more restored in CPU‐6‐grafted animals as compared to CPU‐2 animals, although the number surviving dopaminergic neurons and dopamine release were similar in the two groups. Furthermore, a correlation analysis revealed a number of inverse relationships between the rate of DA neuron survival and sensorimotor performances, e.g., for skilled forelimb use. DA grafts placed into the NAc induced a partial recovery in drug‐induced rotation tests but failed to restore any of the other sensorimotor behaviors tested. Taken together, these data have important implications both for a better understanding of the complex functional graft–host interactions as well as for the further optimization of clinical neural transplantation strategies in neurodegenerative diseases. J. Comp. Neurol. 515:41–55, 2009. © 2009 Wiley‐Liss, Inc.