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Author Notes:

Address correspondence to: Jessica Raper, Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA, 30329. Phone: (404)727-8334, jraper@emory.edu

Authors are grateful to Dr. Arthur Merrill Sr and Mrs. Sarah Merrill (The Arthur and Sarah Merrill Foundation) for their generous donation which made the current study possible.

Additional thanks goes to Malu Tansey, Ph.D. in the Emory Multiplexed Immunoassay Core for assistance with the cytokine assays and Jonathan Lowe, B.S. in the Yerkes Biomarker Core for assistance with the cortisol assay.

Last, but certainly not least, special thanks Nancy Bliwise, Ph.D. and Donghai Liang, M.P.H. for their statistical advice and expertise.

No conflicts of interest.

Subjects:

Research Funding:

This research was supported by the Merrill Huntington’s Disease Pilot Grant Program at Emory University (00023988) and the Transgenic Huntington’s Disease Monkey Resource sponsored by the Office of Research Infrastructure Programs (ORIP) OD010930.

Yerkes National Primate Research Center is supported by the National Institutes of Health, Office of Research Infrastructure Programs (ORIP/OD) P51-OD011132.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Neurosciences
  • Neurosciences & Neurology
  • Emotion
  • Cytokines
  • Inflammation
  • IL-6
  • TNF-alpha
  • ISGs
  • PITUITARY-ADRENAL AXIS
  • INFANT RHESUS MACAQUES
  • GENE CARRIERS
  • MUTATION CARRIERS
  • MACACA-MULATTA
  • PSYCHIATRIC-SYMPTOMS
  • DEFENSIVE BEHAVIORS
  • CAG REPEATS
  • ONSET
  • PREMANIFEST

Increased irritability, anxiety, and immune reactivity in transgenic Huntington's disease monkeys

Tools:

Journal Title:

Brain, Behavior, and Immunity

Volume:

Volume 58

Publisher:

, Pages 181-190

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Although the most notable clinical symptoms of Huntington's disease (HD) are motor disturbances and brain atrophy, other symptoms include cognitive dysfunction, emotional and hormonal dysregulation. Emotional dysregulation (irritability, anger/aggression, and anxiety) and increased inflammation are early emerging symptoms which can be detected decades before the onset of motor symptoms in HD patients. Despite the advances in understanding the genetic causes of HD there is still no cure or preventative treatment. Thus, to better understand the pathogenesis of HD and develop effective treatments, a holistic understanding of HD is needed, as well as animal models that replicate the full spectrum of HD symptoms. The current study examined the emotional, hormonal, and gene expression responses to an acute stressor of adult male transgenic HD rhesus monkeys (n = 2) as compared to wild-type controls (n = 2). Results revealed that HD monkeys expressed increased anxiety and irritability/aggression as compared to controls. Reactive cortisol response to the stressor was similar between groups. However, HD monkeys exhibited increased pro-inflammatory cytokines and higher induction of immune pathway genes as compared to controls. Overall, results reveal that HD monkeys exhibit these early emerging symptoms of HD and may be an effective animal model to facilitate the development of new therapeutics for HD patients.

Copyright information:

© 2016 Elsevier Inc. All rights reserved.

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