title: Increased irritability, anxiety, and immune reactivity in transgenic Huntington's disease monkeys.
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.
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA; Department of Psychology, Emory University, 36 Eagle Row, Atlanta, GA 30322, USA. Electronic address: jraper@emory.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Raper
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA. Electronic address: steven.bosinger@emory.edu.
authors.forename: Steven
authors.initials: S
authors.lastname: Bosinger
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA. Electronic address: zpjohns@emory.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Johnson
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA. Electronic address: gktharp@emory.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Tharp
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA. Electronic address: sean.p.moran@vanderbilt.edu.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Moran
authors.affiliation: Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA; Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA. Electronic address: awchan@emory.edu.
authors.forename: Anthony W S
authors.initials: AWS
authors.lastname: Chan
mesh_terms: D000374:Aggression; D000818:Animals; D030801:Animals, Genetically Modified; D001007:Anxiety; D001522:Behavior, Animal; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006816:Huntington Disease / Q000235:genetics / Q000276:immunology* / Q000523:psychology*; D006854:Hydrocortisone / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D006854:Hydrocortisone
keywords: Cytokines; Emotion; IL-6; ISGs; Inflammation; TNF-ɑ