β2⁎ and β4⁎ nicotinic acetylcholine receptor expression changes with progressive parkinsonism in non-human primates

Neurobiology of Disease

Hong Fan¹  Jay S. Schneider²  Jennifer M. Kulak³ 

[1] Corresponding author. Fax: [phone].;Johns Hopkins University, Department of Radiology, Baltimore, MD, USA;Thomas Jefferson University, Department of Pathology, Anatomy and Cell Biology, 1020 Locust St., 521 JAH Philadelphia, PA 19107, USA;

关键词: Macaca fascicularis;    Macaca mulatta;    Macaca nemestrina;    Epibatidine;    A85380;   

DOI  :  

来源: DOAJ

【 摘 要 】

Autoradiography was used to investigate nicotinic acetylcholine receptor (nAChR) binding in the brains of two groups of macaque monkeys with parkinsonism produced by different types of MPTP exposure: animals with cognitive deficits but no motor symptoms (motor-asymptomatic) and animals with typical motor symptoms of parkinsonism (motor-symptomatic). Motor-asymptomatic animals had no significant changes in [125I]epibatidine binding to β2⁎–β4⁎ nAChRs and [125I]A85380 binding to β2⁎ nAChRs in cognition-related cortical regions such as Broadman’s area 46, orbitofrontal cortex, the anterior cingulate sulcus and the hippocampus, but binding of both radioligands was decreased 70–80% in the caudate and putamen. Motor-symptomatic animals had decreases in β2⁎ and β4⁎ nAChR in the principal sulcus (40–60%), anterior cingulate sulcus (30–55%), and orbitofrontal cortex (30–41%), but not in the hippocampus, plus significant decreases in binding (70–80%) in the caudate and putamen. These results suggest that while nAChR expression is similarly decreased in the striatum of motor-asymptomatic and motor-symptomatic MPTP-treated monkeys, there are differences in β2⁎ and β4⁎ nAChR expression in cortical regions in these two conditions. Therefore, our data suggest that a therapeutic strategy based on nAChR agonist administration that might improve cognition in early PD patients may, due to a changing nAChR profile, have little or no effect on the same symptoms in more advanced patients.

【 授权许可】

Unknown