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Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors.
Neuroscience. 2016 May 13; 322:129-37.N

Abstract

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined.

Authors+Show Affiliations

Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: kuixu@hotmail.com.Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: dilucadaniel@gmail.com.Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: orrumarco@gmail.com.Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: xuy@helix.mgh.harvard.edu.Department of Neurology, 715 Albany Street, C314, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address: chenjf@bu.edu.Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: michaels@helix.mgh.harvard.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

26905951

Citation

Xu, K, et al. "Neuroprotection By Caffeine in the MPTP Model of Parkinson's Disease and Its Dependence On Adenosine A2A Receptors." Neuroscience, vol. 322, 2016, pp. 129-37.
Xu K, Di Luca DG, Orrú M, et al. Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors. Neuroscience. 2016;322:129-37.
Xu, K., Di Luca, D. G., Orrú, M., Xu, Y., Chen, J. F., & Schwarzschild, M. A. (2016). Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors. Neuroscience, 322, 129-37. https://doi.org/10.1016/j.neuroscience.2016.02.035
Xu K, et al. Neuroprotection By Caffeine in the MPTP Model of Parkinson's Disease and Its Dependence On Adenosine A2A Receptors. Neuroscience. 2016 May 13;322:129-37. PubMed PMID: 26905951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors. AU - Xu,K, AU - Di Luca,D G, AU - Orrú,M, AU - Xu,Y, AU - Chen,J-F, AU - Schwarzschild,M A, Y1 - 2016/02/22/ PY - 2015/06/25/received PY - 2016/02/16/revised PY - 2016/02/17/accepted PY - 2016/2/25/entrez PY - 2016/2/26/pubmed PY - 2016/12/15/medline KW - MPTP KW - adenosine A(2A) receptors KW - caffeine KW - neuroprotection KW - parkinson’s disease SP - 129 EP - 37 JF - Neuroscience JO - Neuroscience VL - 322 N2 - Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/26905951/Neuroprotection_by_caffeine_in_the_MPTP_model_of_parkinson's_disease_and_its_dependence_on_adenosine_A2A_receptors_ DB - PRIME DP - Unbound Medicine ER -