Neuroinflammation in the living brain of Parkinson's disease.
Evidence shows that neuronal injury accompanies neuroinflammatory reactions in the brain, and well as in Parkinson's disease (PD) animal models, in which the loss of dopamine neurons is associated with the activation of microglia in the substantia nigra. Activated microglia can be illustrated in vivo using Positron emission tomography and [(11)C](R)-PK11195. However, this tracer cannot distinguish between the two aspects of microglial function (protective and inflammatory). To solve this problem, we can use a dopamine transporter marker, [(11)C]CFT, which binds to the dopamine transporter. The binding of the tracer reflects the viability of the presynaptic dopaminergic neurons, as reported in a multicenter trial using single photon emission tomography (SPECT) with [(123I)]beta-CIT, a SPECT version of [(11)C]CFT. In early drug-naïve PD patients, these two tracers showed a unique pattern of binding, [(11)C](R)-PK11195 binding potential in the midbrain was correlated inversely with [(11)C]CFT binding in the putamen, and midbrain [(11)C](R)-PK11195 binding was found to be positively correlated with the motor severity of parkinsonism. These results indicate that early introduction of a neuroprotective drug to suppress microglial activation is favorable in PD and that [(11)C](R)-PK11195 can be used to monitor the progression of the disease. As the disease progressed, the [(11)C]CFT binding was further decreased, and the microglial activation spread over the entire brain. This paper briefly summarizes the neuroinflammation induced by microglia in PD and describes an in vivo aspect of the neuroinflammation in the PD brain by focusing on the covarying changes in microglial activation and neuronal damage.
Ouchi
Yasuomi
Y
Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. ouchi@hama-med.ac.jp
Yagi
Shunsuke
S
Yokokura
Masamichi
M
Sakamoto
Masanobu
M
D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D003042:Cocaine / Q000031:analogs & derivatives; D016207:Cytokines / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000209:etiology*; D006801:Humans; D007546:Isoquinolines; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D016207:Cytokines; D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines; D019275:Radiopharmaceuticals; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; C037850:PK 11195