Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson's disease

Department of Neurology, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Experimental Neurology (Impact Factor: 4.7). 01/2012; 234(2):482-7. DOI: 10.1016/j.expneurol.2012.01.022
Source: PubMed


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.

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    • "Galantamine is used to treat patients with Alzheimer's disease (Houghton and Howes, 2005). The psychoactive effects of caffeine are well known, and recent findings further suggest that caffeine consumption can enhance synaptic plasticity/learning and memory, and may help forestall neurodegeneration in Alzheimer's and Parkinson's diseases (Laurent et al., 2014; Sallaberry et al., 2013; Sonsalla et al., 2012). Psilocybin is an alkaloid present in numerous species of mushroom in the genus Psilocybe, and is widely known as a potent hallucinogen that acts as a partial agonist of serotonin receptors. "
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    • "Decreased activity in the basal ganglia is thought to underlie some of the primary symptoms (tremor, bradykinesia) that are observed in Parkinson’s disease. Experimentally, a number of studies have shown that adenosine receptor antagonists can reduce tremor, improve motor output and may even be neuroprotective [78]–[80], and for this reason these receptors have been targets for the treatment of parkinsonism. It is interesting that in this study, the mouse strains that had lower levels of ADO are those that are generally more sensitive to xenobiotic agents used in modeling of Parkinson’s disease, including MPTP and paraquat [81]–[84]. "
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    • "It is important to note that a caffeine tolerance does not develop with long-term exposure in mice (Xu et al., 2002) and neuroprotection is still apparent with caffeine intake after the onset of neurodegeneration in rats (Sonsalla et al., 2012). Genetic and pharmacological data from rodent studies indicate that caffeine reduces dopaminergic toxicity and slows disease progression through antagonism of adenosine A 2A receptors (Morelli et al., 2010; Prediger, 2010; Xiao et al., 2011; Sonsalla et al., 2012). Inhibition of glutamate neurotransmission using A 2A receptor antagonists, may relieve motor symptoms and provide neuroprotection in models of late-stage PD (reviewed in Popoli et al., 2004; Chen et al., 2007b). "
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