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Decrease of mGluR5 receptor density goes parallel with changes in enkephalin and substance P immunoreactivity in Huntington’s disease: a preliminary investigation in the postmortem human brain

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Abstract

Group 1 metabotropic glutamate subtype 5 receptors (mGluR5) contribute to the control of 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 may occur in Huntington’s disease (HD) and aimed at testing this hypothesis in a preliminary experimental series in postmortem human brain material obtained from HD patients. Using autoradiography, we analyzed mGluR5 density in the putamen, caudate nucleus and cerebellum (control region) in postmortem tissue samples from three patients with HD and three controls with two mGluR5-specific radioligands ([3H]ABP688 and [11C]ABP688). The density of enkephalin (Enk)- or substance P (SP)-containing neurons was assessed using immunohistochemical and cell-counting methods. [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) vs 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 vs 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 vs controls (P < 0.001). In contrast to earlier observations in PD, in HD, compared to controls, the mGluR5 density was significantly lower in the caudate nucleus. The decrease in neuronal density suggests that neuronal loss was largely responsible for the observed decrease in mGluR5.

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Acknowledgments

The authors acknowledge the assistance of the Netherlands Brain Bank, Netherlands Institute for Neuroscience, Amsterdam, for obtaining human brain tissue, and sincerely thank Siv Eriksson and Viktoria Varga for their excellent technical assistance.

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Authors and Affiliations

  1. Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden

    Balázs Gulyás, Zhisheng Jia & Christer Halldin

  2. Novartis Pharma AG, Basel, Switzerland

    Judit Sovago, Martin Schumacher & Ralph Paul Maguire

  3. Novartis Institutes for Biomedical Research, Basel, Switzerland

    Baltazar Gomez-Mancilla & Fabrizio Gasparini

  4. Department of Cell Biology and Molecular Medicine, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary

    Csaba Szigeti & Károly Gulya

Authors
  1. Balázs Gulyás
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  2. Judit Sovago
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  3. Baltazar Gomez-Mancilla
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  4. Zhisheng Jia
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  5. Csaba Szigeti
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  6. Károly Gulya
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  7. Martin Schumacher
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  8. Ralph Paul Maguire
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  9. Fabrizio Gasparini
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  10. Christer Halldin
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Corresponding author

Correspondence to Balázs Gulyás.

Additional information

B. Gulyás and J. Sovago contributed equally to this work.

F. Gasparini and C. Halldin contributed equally to this work.

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Gulyás, B., Sovago, J., Gomez-Mancilla, B. et al. Decrease of mGluR5 receptor density goes parallel with changes in enkephalin and substance P immunoreactivity in Huntington’s disease: a preliminary investigation in the postmortem human brain . Brain Struct Funct 220, 3043–3051 (2015). https://doi.org/10.1007/s00429-014-0812-y

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