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Acta Neuropathologica

, Volume 120, Issue 6, pp 777–788 | Cite as

Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses

  • Sanaz Gabery
  • Karen Murphy
  • Kristofer Schultz
  • Clement T. Loy
  • Elizabeth McCusker
  • Deniz Kirik
  • Glenda Halliday
  • Åsa PetersénEmail author
Original Paper

Abstract

Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been limited assessment of other hypothalamic cell populations that may be involved. In this study, we quantified the neuropeptide-expressing hypothalamic neurons known to regulate metabolism and emotion in patients with HD compared to healthy controls using unbiased stereological methods. We confirmed the loss of orexin-expressing neurons in HD and revealed substantial differences in the peptide expression of other neuronal populations in the same patients. Both oxytocin- and vasopressin-expressing neurons were decreased by 45 and 24%, respectively, while the number of cocaine- and amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in cerebrospinal fluid from HD patients. There was no difference in the numbers of neuropeptide Y-expressing neurons. These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. They may be important in the development of psychiatric symptoms and metabolic disturbances in HD, and may provide potential targets for therapeutic interventions.

Keywords

Huntingtin Neuroendocrine Hypothalamus Orexin Oxytocin Vasopressin CART NPY 

Notes

Acknowledgments

Human brain samples were obtained from the Sydney Brain Bank at Neuroscience Research Australia and the New South Wales Tissue Resource Centre at the University of Sydney, Australia (approved requests PID073 and PID0111 to GH), which are part of the Australian Brain Bank Network supported by the National Health and Medical Research Council in Australia. The Sydney Brain Bank also receives infrastructure support from Neuroscience Research Australia and the University of New South Wales, and the New South Wales Tissue Resource Centre also receives support from The University of Sydney, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health. This study was supported by grants from the Swedish Research Council, Torsten and Ragnar Soderberg Foundation, ALF, Bagadilico, the Crafoord Foundation, The National Board of Health and Welfare in Sweden, Thure Carlsson Foundation, Kjell and Marta Beijer Foundation, Professor Bror Gadelius Foundation, Lindhaga Foundation and the Royal Physiographic Society. GH is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia (Fellowship Grant #630434). We are grateful to Dr Michael Kuhar for the donation of the CART antibody. We thank Catherine O’Connor, Ulla Samuelsson and Sara Wiehager for technical expertise.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sanaz Gabery
    • 1
  • Karen Murphy
    • 2
  • Kristofer Schultz
    • 1
  • Clement T. Loy
    • 2
    • 3
    • 4
  • Elizabeth McCusker
    • 3
  • Deniz Kirik
    • 5
  • Glenda Halliday
    • 2
  • Åsa Petersén
    • 1
    Email author
  1. 1.Translational Neuroendocrine Research Unit, Department of Experimental Medical SciencesLund UniversityLundSweden
  2. 2.Neuroscience Research Australia and the University of New South WalesSydneyAustralia
  3. 3.Huntington Disease ServiceWestmead HospitalSydneyAustralia
  4. 4.Sydney School of Public HealthThe University of SydneySydneyAustralia
  5. 5.Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S.) Unit, Department of Experimental Medical SciencesLund UniversityLundSweden

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