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Changes in mGluR5 density, and enkephalin and substance P immunoreactivity in Huntington’s disease

Gulyas, Balazs and Sovago, Judit and Gomez-Mancilla, Baltazar and Jia, Zhisheng and Gulya, Karoly and Szigeti, Csaba and Schumacher, Martin and Maguire, Paul and Gasparini, Fabrizio and Halldin, Christer (2014) Changes in mGluR5 density, and enkephalin and substance P immunoreactivity in Huntington’s disease. Brain Structure and Function.

Abstract

Background Group 1 metabotropic glutamate subtype 5 receptors (mGluR5) help control motor behavior by regulating the balance between excitation and inhibition of outputs in the basal ganglia. The density of these receptors is increased in patients with Parkinson’s disease and motor complications. We hypothesized that similar changes occur in Huntington’s disease (HD).
Methods We analyze mGluR5 density in the putamen, caudate nucleus and cerebellum (control region) from postmortem tissue samples from three patients with HD and three controls with mGluR5-specific radioligands ([3H]ABP688 and [11C]ABP688). The density of enkephalin (Enk)- or substance P (SP)-containing neurons was assessed using immunohistochemical and stereological methods.
Results [3H]ABP688 binding in HD was reduced in the caudate (-70.4%, P < 0.001), in the putamen (-33.3%, P = 0.053), and in the cerebellum (-8.79%, P = 0.930) versus controls. Results with [11C]ABP688 were similar; there was good correlation between [11C]ABP688 and [3H]ABP688 binding ratios. Total cell density was similar in all three brain regions in HD patients and controls. Neuronal density was 69% lower in the caudate (P = 0.002) and 64% lower in the putamen (P < 0.001) of HD patients versus controls. Both direct and indirect pathways were affected, with ≥ 90% decrease in the density of Enk- and SP-containing neurons in the caudate and putamen of HD patients versus controls (P < 0.001).
Conclusion The mGluR5 density was significantly lower in HD caudate than in controls. The decrease in neuronal density suggests that neuronal loss was largely responsible for the observed decrease in mGluR5.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/20417

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