title: Impaired endoplasmic reticulum stress response in bipolar disorder: cellular evidence of illness progression.
abstract: Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Pfaffenseller
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Wollenhaupt-Aguiar
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Gabriela Delevati
authors.initials: GD
authors.lastname: Colpo
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Renan Kubiachi
authors.initials: RK
authors.lastname: Burque
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Giovana
authors.initials: G
authors.lastname: Bristot
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Pâmela
authors.initials: P
authors.lastname: Ferrari
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Keila Maria Mendes
authors.initials: KM
authors.lastname: Ceresér
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Adriane Ribeiro
authors.initials: AR
authors.lastname: Rosa
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Klamt
authors.affiliation: Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre,Universidade Federal do Rio Grande do Sul,Porto Alegre, RS,Brazil.
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology*; D016022:Case-Control Studies; D002470:Cell Survival; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014415:Tunicamycin; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D014415:Tunicamycin; D051742:Transcription Factor CHOP; C101003:ELF2 protein, human