title: Isolation rearing impaired sensorimotor gating but increased pro-inflammatory cytokines and disrupted metabolic parameters in both sexes of rats.
abstract: Social isolation rearing (SIR) is an early stress paradigm of deprivation of the social contact since weaning. SIR has been used to investigate the mechanisms behind certain mental illnesses with neurodevelopmental origins, including schizophrenia. In schizophrenia, metabolic dysfunction has become a critical issue with increasing evidence for a possible connection between metabolism and immune systems in which metabolic changes are associated with pro-inflammatory cytokine (pro-CK) levels. The present study employed a rat model of SIR with both sexes to examine behaviors [locomotor activity and prepulse inhibition (PPI)], inflammatory markers [C-reactive protein, interleukin (IL)-1 beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and interferon-gamma], and metabolism-related variables (body weight, blood pressure, and the profiles of glycemia and lipid). Our results revealed that around puberty, SIR rats of both sexes exhibited behaviorally a higher locomotor activity and a lower PPI performance. Biochemically, SIR rats had an elevated level of pro-CKs (IL-1 beta, IL-6, TNF-alpha, and interferon-gamma), and metabolic abnormalities (increased insulin resistance, decreased insulin sensitivity, and high blood pressure) in a time-dependent manner. The relationships between pro-CKs and metabolism were sex specific as IL-1 beta and interferon-gamma were correlated to glycemia metabolic indexes in males. The present study demonstrated SIR-induced longitudinal concomitant changes of pro-CKs and metabolic abnormalities, implying a more direct role of these two things in mental dysfunctions with a developmental origin.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Ko
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan. Electronic address: yiaping@ms75.hinet.net.
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001835:Body Weight; D002097:C-Reactive Protein / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D050356:Lipid Metabolism; D008297:Male; D008426:Maternal Deprivation; D009043:Motor Activity; D065808:Prepulse Inhibition; D051381:Rats; D012559:Schizophrenia / Q000276:immunology* / Q000378:metabolism; D012565:Schizophrenic Psychology; D055139:Sensory Gating; D012737:Sex Factors; D012934:Social Isolation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001786:Blood Glucose; D016207:Cytokines; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D002097:C-Reactive Protein
keywords: Cytokines; Development; Metabolic abnormalities; Schizophrenia; Sex; Social isolation rearing