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Self-injurious behaviours in rhesus macaques: Potential glial mechanisms.

ABSTRACT: BACKGROUND:Self-injurious behaviour (SIB) can be classified as intentional, direct injuring of body tissue usually without suicidal intent. In its non-suicidal form it is commonly seen as a clinical sign of borderline personality disorder, autism, PTSD, depression, and anxiety affecting a wide range of ages and conditions. In rhesus macaques SIB is most commonly manifested through hair plucking, self-biting, self-hitting, and head banging. SIB in the form of self-biting is observed in approximately 5-15% of individually housed monkeys. Recently, glial cells are becoming recognised as key players in regulating behaviours. METHOD:The goal of this study was to determine the role of glial activation, including astrocytes, in macaques that had displayed SIB. To this end, we performed immunohistochemistry and next generation sequence of brain tissues from rhesus macaques with SIB. RESULTS:Our studies showed increased vimentin, but not nestin, expression on astrocytes of macaques displaying SIB. Initial RNA Seq analyses indicate activation of pathways involved in tissue remodelling, neuroinflammation and cAMP signalling. CONCLUSIONS:Glia are most probably activated in primates with self-injury, and are therefore potential novel targets for therapeutics.

SUBMITTER: Ramsey J

PROVIDER: S-EPMC6385863 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Self-injurious behaviours in rhesus macaques: Potential glial mechanisms.

Ramsey J J Martin E C EC Purcell O M OM Lee K M KM MacLean A G AG

Journal of intellectual disability research : JIDR 20181201 12

<h4>Background</h4>Self-injurious behaviour (SIB) can be classified as intentional, direct injuring of body tissue usually without suicidal intent. In its non-suicidal form it is commonly seen as a clinical sign of borderline personality disorder, autism, PTSD, depression, and anxiety affecting a wide range of ages and conditions. In rhesus macaques SIB is most commonly manifested through hair plucking, self-biting, self-hitting, and head banging. SIB in the form of self-biting is observed in ap ...[more]

PMID: 30450801

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Project description:Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009, respectively). We also tested the efficacy of guanfacine, an α2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P=0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (rs=-0.761, P=0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans.

Dataset Information

Self-injurious behaviours in rhesus macaques: Potential glial mechanisms.

Publications

Self-injurious behaviours in rhesus macaques: Potential glial mechanisms.

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