ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.
Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.
Department of Neurology, RWTH Aachen University, Aachen, Germany.
Daniel
D
Komnig
Institute of Physiology, RWTH Aachen University, Aachen, Germany.
Silke
S
Imgrund
Department of Neurology, RWTH Aachen University, Aachen, Germany.
Arno
A
Reich
Institute of Physiology, RWTH Aachen University, Aachen, Germany.
Stefan
S
Gründer
Department of Neurology, RWTH Aachen University, Aachen, Germany.|JARA BRAIN Institute II, Jülich and Aachen, Germany.
Björn H
BH
Falkenburger
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D002395:Catecholamines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine