Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson's disease.
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.
Department of Neurology, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. sonsalla@umdnj.edu
Patricia K
PK
Sonsalla
Lai-Yoong
LY
Wong
Suzan L
SL
Harris
Jason R
JR
Richardson
Ida
I
Khobahy
Wenhao
W
Li
Bharathi S
BS
Gadad
Dwight C
DC
German
D000818:Animals; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D004195:Disease Models, Animal; D018450:Disease Progression; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology
D002110:Caffeine