title: Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats.
abstract: Early life stressors in rodents, including maternal separation and social isolation, have been shown to disrupt brain development and profoundly affect a wide-range of behaviors in adult animals. In this study, we focus on the development of female Sprague-Dawley rats in the presence and absence of conspecifics during the critical period of social play. Similar studies in male rodents have shown that this form of social deprivation results in dysregulated dopaminergic and serotonergic functions in the brain with core features of neuropsychiatric disorders including anxiety disorder and schizophrenia. Here we examined the behavioral and biochemical effects of post-weaning social isolation in female rats. Our findings demonstrated that isolation rearing produced marked deficits in social interaction behaviors and increased anxiety in open-field and novelty-suppressed feeding tests. The expression of synaptic-associated proteins PSD95 and synapsin I as well as glutamate receptors subunits GluR1 and NR1 in the prefrontal cortex (PFC) were significantly reduced in isolation-reared female rats. Current findings provide evidence that in female rats, post-weaning environmental disruption can result in profound dysregulation of synapse-related proteins and behavior.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Gretchen.hermes@yale.edu
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hermes
authors.forename: Nanxin
authors.initials: N
authors.lastname: Li
authors.forename: Catharine
authors.initials: C
authors.lastname: Duman
authors.forename: Ronald
authors.initials: R
authors.lastname: Duman
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001526:Behavioral Symptoms / Q000209:etiology* / Q000473:pathology*; D001835:Body Weight; D000076122:Disks Large Homolog 4 Protein; D004964:Estriol / Q000378:metabolism; D004971:Estrus / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012934:Social Isolation / Q000523:psychology*; D016704:Synapsins / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D004964:Estriol; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; C501449:Dlg4 protein, rat; C409466:NR1 NMDA receptor