title: Pair housing reverses post-stroke depressive behavior in mice.
abstract: Social isolation (SI) has been linked epidemiologically to high rates of morbidity and mortality following stroke. In contrast, strong social support enhances recovery and lowers stroke recurrence. However, the mechanism by which social support influences stroke recovery has not been adequately explored. The goal of this study was to examine the effect of post-stroke pair housing and SI on behavioral phenotypes and chronic functional recovery in mice. Young male mice were paired for 14 days before a 60 min transient middle cerebral artery occlusion (MCAO) or sham surgery and assigned to various housing environments immediately after stroke. Post-stroke mice paired with either a sham or stroke partner showed significantly higher (P<0.05) sociability after MCAO than isolated littermates. Sociability deficits worsened over time in isolated animals. Pair-housed mice showed restored sucrose consumption (P<0.05) and reduced immobility in the tail suspension test compared to isolated cohorts. Pair-housed stroked mice demonstrated significantly reduced cerebral atrophy after 6 weeks (17.5 ± 1.5% in PH versus 40.8 ± 1.3% in SI; P<0.001). Surprisingly, total brain arginase-1, a marker of a M2 "alternatively activated" myeloid cells was higher in isolated mice. However, a more detailed assessment of cellular expression showed a significant increase in the number of microglia that co-labeled with arginase-1 in the peri-infarct region in PH stroke mice compared to SI mice. Pair housing enhances sociability and reduces avolitional and anhedonic behavior. Pair housing reduced serum IL-6 and enhanced peri-infarct microglia arginase-1 expression. Social interaction reduces post-stroke depression and improves functional recovery.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Friedler
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Nia M
authors.initials: NM
authors.lastname: Harris
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA; Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA. Electronic address: lmccullough@uchc.edu.
authors.forename: Louise D
authors.initials: LD
authors.lastname: McCullough
mesh_terms: D059445:Anhedonia / Q000502:physiology; D000818:Animals; D001119:Arginase / Q000378:metabolism; D001284:Atrophy; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D006799:Housing, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology; D012919:Social Behavior; D012934:Social Isolation; D013997:Time Factors
chemical_list: D019422:Dietary Sucrose; D015850:Interleukin-6; C577686:interleukin-6, mouse; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: Arginase-1; IL-6; Ischemic stroke; Post stroke depression; Sociability; Social isolation