%0 Journal Article
%T ¦Á
%A Iliana Hernandez
%A Marina E. Emborg
%A Scott C. Vermilyea
%A Scott Guthrie
%A Viktorya Bondarenko
%J Cell Transplantation
%@ 1555-3892
%D 2019
%R 10.1177/0963689719835794
%X ¦Á-Synuclein (¦Á-syn) is a small presynaptic protein distributed ubiquitously in the central and peripheral nervous system. In normal conditions, ¦Á-syn is found in soluble form, while in Parkinson¡¯s disease (PD) it may phosphorylate, aggregate, and combine with other proteins to form Lewy bodies. The purpose of this study was to evaluate, in nonhuman primates, whether ¦Á-syn expression is affected by age and neurotoxin challenge. Young adult (n = 5, 5¨C10 years old) and aged (n = 4, 23¨C25 years old) rhesus monkeys received a single unilateral carotid artery injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Three months post-MPTP the animals were necropsied by transcardiac perfusion, and their brains extracted and processed with immunohistochemical methods. Quantification of tyrosine hydroxylase (TH)-positive substantia nigra (SN) neurons showed a significant 80¨C89% decrease in the side ipsilateral to MPTP administration in young and old animals. Optical density of TH- immunoreactivity (-ir) in the caudate and putamen presented a 60¨C70% loss compared with the contralateral side. ¦Á-Syn-ir was present in both ipsi- and contra- lateral MPTP-treated nigra, caudate, and putamen, mostly in fibers; its intracellular distribution was not affected by age. Comparison of ¦Á-syn-ir between MPTP-treated young and aged monkeys revealed significantly higher optical density for both the ipsi- and contralateral caudate and SN in the aged animals. TH and ¦Á-syn immunofluorescence confirmed the loss of nigral TH-ir dopaminergic neurons in the MPTP-treated side of intoxicated animals, but bilateral ¦Á-syn expression. Colabeling of GAD67 and ¦Á-syn immunofluorescence showed that ¦Á-syn expression was present mainly in GABAergic fibers. Our results demonstrate that, 3 months post unilateral intracarotid artery infusion of MPTP, ¦Á-syn expression in the SN is largely present in GABAergic fibers, regardless of age. Bilateral increase of ¦Á-syn expression in SN fibers of aged, compared with young rhesus monkeys, suggests that ¦Á-syn-ir may increase with age, but not after neurotoxin-induced dopaminergic nigral cell loss
%K Parkinson¡¯s disease
%K nonhuman primate
%K alpha-synuclein
%K tyrosine hydroxylase
%K age
%K MPTP
%U https://journals.sagepub.com/doi/full/10.1177/0963689719835794