Dopaminergic Denervation and Spine Loss in the Striatum of MPTP-treated Monkeys.

• Type of Material: Article
• Authors: Rosa Villalba, Emory University; Heyne Lee, Emory University; Yoland Smith, Emory University
• Language: English
• Date: 2009-02
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009, Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2008.09.025
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 215
• Issue: 2
• Start Page: 220
• End Page: 227
• Grant/Funding Information: This research was supported by NIH grant R01 NS 037948 to Y. Smith and the NIH base grant to the Yerkes National Primate Research Center (RR 00165).
• Keywords: Golgi-impregnation; spine plasticity; MPTP-model; dopamine receptors; Parkinson's disease; immunocytochemistry
• Research Categories: Biology, Neuroscience; Health Sciences, General

Abstract

Striatal spine loss is a key pathological feature of human Parkinson’s disease (PD) that can be induced after complete degeneration of the nigrostriatal dopaminergic system in rodent models of parkinsonism. In line with these observations, our findings reveal a significant (30–50%) reduction in spine density in both the caudate nucleus and putamen of severely DA-depleted striata of MPTP-treated monkeys; the sensorimotor post-commissural putamen being the most severely affected region for both dopamine depletion and spine loss. Using MPTP-treated monkeys with complete or partial striatal dopamine (DA) denervation, we also demonstrate that striatal spine loss is an early pathological feature of parkinsonism, which progresses along a positive rostrocaudal and mediolateral gradient in parallel with the extent of striatal dopamine denervation. Quantitative electron microscopy immunocytochemistry for D1 dopamine receptor (D1) in the striatum of control and severely DA-depleted animals revealed that both D1-immunoreactive and immunonegative spines are lost in the putamen of MPTP-treated monkeys. These data demonstrate that striatal spine loss in MPTP-treated monkeys is an early pathological event of parkinsonism, tightly correlated with the degree of nigrostriatal dopamine denervation that likely affects both direct and indirect striatofugal pathways.