title: Reversal of the Detrimental Effects of Post-Stroke Social Isolation by Pair-Housing is Mediated by Activation of BDNF-MAPK/ERK in Aged Mice.
abstract: Social isolation (SI) increases stroke-related mortality and morbidity in clinical populations. The detrimental effects of SI have been successfully modeled in the laboratory using young animals. Mechanistically, the negative effects of SI in young animals are primarily mediated by an enhanced inflammatory response to injury and a reduction in neurotrophic factors. However, the response to brain injury differs considerably in the aged. Given that SI is more prevalent in aged populations, we hypothesized that isolation, even when initiated after stroke, would delay recovery in aged mice. We found that aged isolated male mice had significantly increased infarct volume, neurological deficits, and serum IL-6 levels three days after stroke compared to pair housed (PH) mice. Using RT(2) Profiler PCR Array and real-time quantitative PCR we found several important synaptic plasticity genes were differentially expressed in post-stroke SI mice. Furthermore, paired mice showed improved memory and neurobehavioral recovery four weeks after injury. Mechanistic and histological studies showed that the beneficial effects of pair housing are partially mediated by BDNF via downstream MAPK/ERK signaling and restoration of axonal basic myelin protein levels.
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: Nia M
authors.initials: NM
authors.lastname: Harris
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: Joshua
authors.initials: J
authors.lastname: Crapser
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Anita R
authors.initials: AR
authors.lastname: Patel
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Venna
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.|Department of Neurology, University of Texas Health Science Center, Houston, TX 77030, USA.
authors.forename: Louise D
authors.initials: LD
authors.lastname: McCullough
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020869:Gene Expression Profiling; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity; D012934:Social Isolation; D020521:Stroke / Q000150:complications* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; C577686:interleukin-6, mouse; D048049:Extracellular Signal-Regulated MAP Kinases