Comparison of the D2 receptor regulation and neurotoxicant susceptibility of nigrostriatal dopamine neurons in wild-type and CB1/CB2 receptor knockout mice.
Motor dysfunctions of Parkinson Disease (PD) are due to the progressive loss of midbrain nigrostriatal dopamine (NSDA) neurons. Evidence suggests a role for cannabinoid receptors in the neurodegeneration of these neurons following neurotoxicant-induced injury. This work evaluates NSDA neurons in CB1/CB2 knockout (KO) mice and tests the hypothesis that CB1/CB2 KO mice are more susceptible to neurotoxicant exposure. NSDA neuronal indices were assessed using unbiased stereological cell counting, high pressure liquid chromatography coupled with electrochemical detection or mass spectrometry, and Western blot. Results reveal that CB1 and CB2 cannabinoid receptor signaling is not necessary for the maintenance of a normally functioning NSDA neuronal system. Mice lacking CB1 and CB2 receptors were found to be equally susceptible to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). These studies support the use of CB1/CB2 KO mice for investigating the cannabinoid receptor-mediated regulation of the NSDA neuronal system in models of PD.
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA. simkinst@msu.edu
Tyrell J
TJ
Simkins
Kelly L
KL
Janis
Alison K
AK
McClure
Bahareh
B
Behrouz
Samuel S
SS
Pappas
Andreas
A
Lehner
Norbert E
NE
Kaminski
John L
JL
Goudreau
Keith J
KJ
Lookingland
Barbara L F
BL
Kaplan
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency*; D043885:Receptor, Cannabinoid, CB2 / Q000172:deficiency*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D065127:Dopamine D2 Receptor Antagonists; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine