Plasticity of nerve afferents to nigrostriatal neurons in Parkinson's disease.
Clinical symptoms in Parkinson's disease do not appear until almost total depletion of dopamine has occurred in the striatum, suggesting the existence of compensatory mechanisms to offset the loss of nigrostriatal dopaminergic neurons. This compensation has been attributed mainly to an increased turnover of dopamine in the remaining dopaminergic neurons. Besides this biochemical phenomenon intrinsic to dopaminergic neurons, we tested whether morphological changes in the nerve afferents to the dopaminergic neurons could participate in these compensatory mechanisms. The afferents to the dendrites of dopaminergic neurons were analyzed ultrastructurally in the substantia nigra of parkinsonian patients and matched controls, using simultaneous histochemical detection of acetylcholine-like cation and tyrosine hydroxylase. The size of acetylcholine-like cation-containing terminals in contact with dopaminergic dendrites increased significantly by 38% in the substantia nigra of parkinsonian patients; whereas their number per section of dopaminergic dendrite showed an increase of 60%, although not reaching statistical significance. The number of the terminals devoid of acetylcholine-like cation per section of dopaminergic dendrite decreased significantly by 52% in the substantia nigra of parkinsonian patients. These results suggest (1) a plasticity of excitatory cholinergic neurons targeting nigral dopaminergic neurons and (2) an involution of noncholinergic nerve terminals, mostly originating from inhibitory nigral, pallidal, and striatal GABAergic neurons. The findings provide evidence of a capacity for neuronal plasticity in the elderly human brain, even in the presence of neurodegenerative disorders.
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
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P
Anglade
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S
Tsuji
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F
Javoy-Agid
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Y
Agid
E C
EC
Hirsch
D000109:Acetylcholine / Q000032:analysis; D000368:Aged; D003342:Corpus Striatum / Q000503:physiopathology*; D003712:Dendrites / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009411:Nerve Endings / Q000737:chemistry; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000503:physiopathology*
D000109:Acetylcholine; D004298:Dopamine