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Plasticity of the nigrostriatal system in MPTP-treated mice. A biochemical and morphological correlation
F F Cruz-Sanchez1, A Cardozo, S Ambrosio
1Neurological Tissue Bank, University of Barcelona, Hospital Clínico y Provincial, Spain.
Abstract:
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 or old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra pars compacta and the striatum were studied using the Golgi method. Immunostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study the glial response. Striatal catecholamines were determined to correlate the biochemical data with the morphological changes. Significant neuronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and distortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodulations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and striatum from all the old treated mice was found. Recovery was only observed in adult mice sacrificed 10 d after withdrawal. At this time, all the old MPTP-treated mice showed marked neuronal changes and a persistent marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animals; at 10 d, the depletion was partially reversed in the adult group. These data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal neuropil constitutes a significant causal factor of the MPTP neurotoxicity. These features are related to the age of the animals and the integrity of the plasticity phenomena, which appear to be altered in old mice.
Insights
MPTP hydrochloride causes neuronal damage in mice, with older mice showing less recovery. This highlights age-related decline in neural plasticity and recovery capacity.
Area of Science:
- Neuroscience
- Toxicology
- Aging Research
Background:
- The nigrostriatal system is crucial for motor control.
- MPTP hydrochloride is a neurotoxin that selectively damages dopaminergic neurons.
- Age significantly impacts the brain's ability to repair and regenerate.
Purpose of the Study:
- To compare the recovery capacity of the nigrostriatal system in adult versus old mice after MPTP hydrochloride administration.
- To investigate the morphological and biochemical changes associated with MPTP neurotoxicity and aging.
- To correlate neuronal and glial responses with functional recovery.
Main Methods:
- MPTP hydrochloride administration to adult and old BL/C57 male mice.
- Morphological analysis using the Golgi method for neurons and cellular processes.
- Immunostaining for glial fibrillary acidic protein to assess glial response.
- Measurement of striatal catecholamines to evaluate biochemical changes.
Main Results:
- MPTP hydrochloride induced significant neuronal and axonal damage in both adult and old mice.
- Old mice exhibited marked persistent gliosis and neuronal changes, with limited recovery.
- Adult mice showed partial recovery of dopamine levels and neuronal morphology 10 days after MPTP withdrawal.
- Significant depletion of dopamine and metabolites was observed 24 hours post-treatment in all groups.
Conclusions:
- Deterioration of dendritic and axonal neuropil is a significant factor in MPTP neurotoxicity.
- Age-related alterations in neural plasticity impair recovery mechanisms in the nigrostriatal system.
- Older mice demonstrate a reduced capacity for repair and regeneration following neurotoxic injury compared to adults.