Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography.
Parkin is the causal gene of autosomal recessive juvenile parkinsonism (AR-JP). Dopamine (DA) metabolism has been linked to Parkinson's disease (PD). To understand the pathogenesis of AR-JP, we generated parkin-deficient mice to assess the status of DA signaling pathway and examine DA release and DA receptor by ex vivo autoradiography. Ex vivo autoradiography using [11C]raclopride showed a clear decrease in endogenous DA release after methamphetamine challenge in parkin-deficient mice. Furthermore, parkin deficiency was associated with considerable upregulation of DA (D1 and D2) receptor binding in vivo in the striatum and increased DA levels in the midbrain. Our results suggest that dopaminergic neurons could behave abnormally before neuronal death.
Sato
Shigeto
S
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Chiba
Tomoki
T
Nishiyama
Shingo
S
Kakiuchi
Takeharu
T
Tsukada
Hideo
H
Hatano
Taku
T
Fukuda
Takahiro
T
Yasoshima
Yasunobu
Y
Kai
Nobuyuki
N
Kobayashi
Kazuto
K
Mizuno
Yoshikuni
Y
Tanaka
Keiji
K
Hattori
Nobutaka
N
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D015139:Blotting, Southern; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000378:metabolism*; D049268:Positron-Emission Tomography; D004856:Postural Balance / Q000502:physiology; D020891:Raclopride / Q000494:pharmacology; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics*
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D020891:Raclopride; D008694:Methamphetamine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004296:Dopa Decarboxylase; D004298:Dopamine