Remodeling of the dendritic structure of the striatal medium spiny neurons accompanies behavioral recovery in a mouse model of Parkinson's disease

초록

Medium spiny neurons (MSNs) are the major type of neurons found in the striatum. The dendritic spines on these cells contain glutamatergic synaptic contacts between the cortex (or the thalamus) and the striatum. The complexity of the dendritic structure of MSNs may therefore reflect the functional status of the basal ganglia because the striatum is the major input structure in which signals from different regions are integrated. We examined the structural alterations in the dendrites of striatal MSNs in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). Acute MPTP treatment rapidly damaged dopaminergic neurons and their terminals within the striatum and caused behavioral impairments. However, mice injected with MPTP spontaneously recovered from these behavioral impairments within one week. This recovery was accompanied by the restoration of dendritic structures on MSNs, but the damage to dopaminergic neurons remained extensive. Furthermore, we demonstrated that rasagiline, a monoamine oxidase-B (MAO-B) inhibitor that has been shown to be efficacious for PD, could enhance the dendritic complexity of cultured MSNs. The effect of rasagiline on the spine-like structures of dendrites, however, appears not to require DA availability because the small protrusions of dendrites in cultured MSNs without major source of DA input was similarly changed by rasagiline. Our data suggest that the dendritic structures of striatal MSNs change dynamically, reflecting the progression of motor-related symptoms in PD, and the restoration of functional synapses in the MSNs of PD patients may constitute a clinical target for symptomatic alleviation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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