Abstract
Idiopathic Parkinson’s disease (PD) is characterized by mesencephalic dopaminergic neuron cell death and striatal dopamine (DA) depletion. The factors involved in the pathogenesis of the disease are still unknown. Transforming growth factor β1 (TGFβ1) is increased in the striatum of patients with PD. However, the effect of this increase is not known. Here, we show that overexpression of TGFβ1, by recombinant adenovirus TGFβ1 gene transfer, in the mesostriatal system of an MPTP mouse model of PD decreased the number of mesencephalic dopaminergic neurons. This effect also involved more extensive DA depletion in the striatum. Striatal enkephalin mRNA levels are augmented, suggesting a decrease in dopaminergic transmission to the postsynaptic target. In the absence of MPTP, TGFβ1 greatly decreased the number of dopaminergic neurons in the ventral mesencephalon of fully mature mice. These results show that an increase in TGFβ1 levels aggravate the parkinsonian status of MPTP mice and may therefore be a risk factor for the development of PD.
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