Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease

URA CNRS-CEA 2210, MIRCen, I2BM/DSV, Orsay, France.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 06/2009; 29(9):1601-8. DOI: 10.1038/jcbfm.2009.74
Source: PubMed


Smoking is associated with a lower incidence of Parkinson's disease (PD), which might be related to a neuroprotective action of nicotine. Postmortem studies have shown a decrease of cerebral nicotinic acetylcholine receptors (nAChRs) in PD. In this study, we evaluated the decrease of nAChRs in PD in vivo using positron emission tomography (PET), and we explored the relationship between nAChRs density and PD severity using both clinical scores and the measurement of striatal dopaminergic function. Thirteen nondemented patients with PD underwent two PET scans, one with 6-[(18)F]fluoro-3,4-dihydroxy-L-phenylalanine (6-[(18)F]fluoro-L-DOPA) to measure the dopaminergic function and another with 2-[(18)F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[(18)F]fluoro-A-85380), a radiotracer with high affinity for the nAChRs. Distribution volumes (DVs) of 2-[(18)F]fluoro-A-85380 measured in the PD group were compared with those obtained from six nonsmoking healthy controls, with regions-of-interest and voxel-based approaches. Both analyses showed a significant (P <0.05) decrease of 2-[(18)F]fluoro-A-85380 DV in the striatum (-10%) and substantia nigra (-14.9%) in PD patients. Despite the wide range of PD stages, no correlation was found between DV and the clinical and PET markers of PD severity.

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Available from: Philippe Remy, Apr 14, 2014
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    • "Several studies in animals have shown that nicotine administration enhances dopaminergic integrity in the striatum, especially when administered before/during but not after nigrostriatal damage (Huang et al., 2011). Indeed, a cholinergic loss does not parallel dopaminergic state in PD patients as measured by means of 18F-DOPA and PET (Kas et al., 2009) or with markers of disease severity (i.e., UPDRS-III), disease duration, and daily dose of l-DOPA and dopamine agonists (i.e., LEDDs) (our study, Bohnen et al., 2006; Oishi et al., 2007; Kas et al., 2009). "
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    • "Using positron emission tomography (PET), or single-photon emission computed tomography (SPECT), it has been revealed that regional metabolism in the resting state is abnormal in PD. The patients have hypermetabolism in some regions, like the globus pallidus, thalamus, and cerebellum, as well as hypometabolism in some other areas including prefrontal cortex, SMA, and parietal cortex [11], [12], [13]. Thus, it is likely that FC in the resting state is also different in PD and normal subjects, and these differences may contribute to the observed higher or lower activity in patients with PD detected by fMRI during task performance. "
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