PLASTICITY OF THE NIGROSTRIATAL SYSTEM IN MPTP-TREATED MICE - A BIOCHEMICAL AND MORPHOLOGICAL CORRELATION

In order to compare the recovery capacity of the nigrostriatal system between adult and old mice, MPTP hydrochloride was administered to 48 BL/C57 male mice, which were sacrificed 24 h or 10 d after the second dose. The animals were divided into four groups, based on age (adult o r old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra par s compacta and the striatum were studied using the Golgi method. Immun ostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study t he glial response. Striatal catecholamines were determined to correlat e the biochemical data with the morphological changes. Significant neu ronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and d istortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodu lations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and stria tum from all the old treated mice was found. Recovery was only observe d in adult mice sacrificed 10 d after withdrawal. At this time, all th e old MPTP-treated mice showed marked neuronal changes and a persisten t marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animal s; at 10 d, the depletion was partially reversed in the adult group. T hese data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal n europil constitutes a significant causal factor of the MPTP neurotoxic ity. These features are related to the age of the animals and the inte grity of the plasticity phenomena, which appear to be altered in old m ice.