title: Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.
abstract: The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors.
authors.affiliation: Tulane National Primate Research Center, Covington, LA, USA; Tulane Program in Biomedical Science, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Tulane National Primate Research Center, Covington, LA, USA; Department of Biomedical Engineering, Tulane University, New Orleans, LA, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Chiu
authors.affiliation: Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.affiliation: Tulane National Primate Research Center, Covington, LA, USA; Department of Psychology, Tulane University, New Orleans, LA, USA; Tulane Program in Neuroscience, Tulane University, New Orleans, LA, USA.
authors.forename: Kate C
authors.initials: KC
authors.lastname: Baker
authors.affiliation: Tulane National Primate Research Center, Covington, LA, USA; Tulane Program in Biomedical Science, Tulane University School of Medicine, New Orleans, LA, USA; Tulane Program in Neuroscience, Tulane University, New Orleans, LA, USA; Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: amaclean@tulane.edu.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: MacLean
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D016728:Self-Injurious Behavior / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D066127:White Matter / Q000187:drug effects / Q000473:pathology
chemical_list: D051195:Toll-Like Receptor 2; D009271:Naltrexone
keywords: Astrocyte; Behavior; Glia; Naltrexone; Plasticity; Self-injury