Journal Article Normative data of dopaminergic neurotransmission functions in substantia nigra measured with MRI and PET: Neuromelanin, dopamine synthesis, dopamine transporters, and dopamine D2 receptors

Ito, Hiroshi  ,  Kawaguchi, Hiroshi  ,  Kawaguchi, Hiroshi  ,  Takuwa, Hiroyuki  ,  Ikoma, Yoko  ,  Shimada, Hitoshi  ,  Kimura, Yasuyuki  ,  Seki, Chie  ,  Kubo, Hitoshi  ,  Ishii, Shiro  ,  Takano, Harumasa  ,  Suhara, Tetsuya

158pp.12 - 17 , 2017-06
The central dopaminergic system is of major importance in thepathophysiology of Parkinson’s disease, schizophrenia, and otherneuropsychiatric disorders. In the present study, the normative data ofdopaminergic neurotransmission functions in the midbrain, consisting ofneuromelanin, dopamine synthesis, dopamine transporters and dopamine D2receptors, were constructed using magnetic resonance (MR) imaging andpositron emission tomography (PET). PET studies with L-[β-11C]DOPA,[18F]FE-PE2I and [11C]FLB457 and MRI studies were performed on healthyyoung men. Neuromelanin accumulation measured by MRI was compared withdopaminergic functions, dopamine synthesis capacity, dopamine transporterbinding and dopamine D2 receptor binding measured by PET in the substantianigra. Although neuromelanin is synthesized from DOPA and dopamine indopaminergic neurons, neuromelanin accumulation did not correlate withdopamine synthesis capacity in young healthy subjects. The role of dopaminetransporters in the substantia nigra is considered to be the transport of dopamineinto neurons, and therefore dopamine transporter binding might be related toneuromelanin accumulation; however, no significant correlation was observedbetween them. A positive correlation between dopamine D2 receptor binding and neuromelanin accumulation was observed, indicating a feedback mechanism by dopaminergic autoreceptors. Discrepancies in regional distribution between neuromelanin accumulation and dopamine synthesis capacity, dopamine transporter binding or dopamine D2 receptor binding were observed in the substantia nigra.

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