Publication year: 2012
Source: Experimental Neurology, Available online 28 January 2012
Patricia K. Sonsalla, Lai-Yoong Wong, Sue L. Harris, Jason R. Richardson, Ida Khobahy, ...
Parkinson's disease (PD) is characterized by a prominent degeneration of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. Despite clinical and preclinical studies of neuroprotective strategies for PD, there is no effective treatment for preventing or slowing the progression of neurodegeneration. The inverse correlation between caffeine consumption and risk of PD suggests that caffeine may exert neuroprotection. Whether caffeine is neuroprotective in a chronic progressive model of PD has not been evaluated nor is it known if delayed caffeine treatment can stop DA neuronal loss. We show that a chronic unilateral intra-cerebroventricular infusion of 1-methyl-4-phenylpyridinium in the rat brain for 28 days produces a progressive loss of DA and tyrosine hydroxylase in the ipsilateral striatum and a loss of DA cell bodies and microglial activation in the ipsilateral substantia nigra. Chronic caffeine consumption prevented the degeneration of DA cell bodies in the substantia nigra. Importantly, neuroprotection was still apparent when caffeine was introduced after the onset of the neurodegenerative process. These results add to the clinical relevance for adenosine receptors as a disease-modifying drug target for PD.
Highlights
► Chronic icv MPP + infusion produces progressive loss of striatal dopamine markers ► Caffeine treatment protects against MPP + − induced loss of nigral dopamine neurons ► Delayed caffeine treatment rescues dopamine neurons from MPP +
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