title: Anxious phenotypes plus environmental stressors are related to brain DNA damage and changes in NMDA receptor subunits and glutamate uptake.
abstract: This study aimed at investigating the effects of chronic mild stress on DNA damage, NMDA receptor subunits and glutamate transport levels in the brains of rats with an anxious phenotype, which were selected to represent both the high-freezing (CHF) and low-freezing (CLF) lines. The anxious phenotype induced DNA damage in the hippocampus, amygdala and nucleus accumbens (NAc). CHF rats subjected to chronic stress presented a more pronounced DNA damage in the hippocampus and NAc. NMDAR1 were increased in the prefrontal cortex (PC), hippocampus and amygdala of CHF, and decreased in the hippocampus, amygdala and NAc of CHF stressed. NMDAR2A were decreased in the amygdala of the CHF and stressed; and increased in CHF stressed. NMDRA2A in the NAc was increased after stress, and decreased in the CLF. NMDAR2B were increased in the hippocampus of CLF and CHF. In the amygdala, there was a decrease in the NMDAR2B for stress in the CLF and CHF. NMDAR2B in the NAc were decreased for stress and increased in the CHF; in the PC NMDAR2B increased in the CHF. EAAT1 increased in the PC of CLF+stress. In the hippocampus, EAAT1 decreased in all groups. In the amygdala, EAAT1 decreased in the CLF+stress and CHF. EAAT2 were decreased in the PC for stress, and increased in CHF+control. In the hippocampus, the EAAT2 were increased for the CLF and decreased in the CLF+stress. In the amygdala, there was a decrease in the EATT2 in the CLF+stress and CHF. These findings suggest that an anxious phenotype plus stress may induce a more pronounced DNA damage, and promote more alterations in the glutamatergic system. These findings may help to explain, at least in part, the common point of the mechanisms involved with the pathophysiology of depression and anxiety.
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA. Electronic address: gislainezilli@hotmail.com.
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Abaleira
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Monique
authors.initials: M
authors.lastname: Michels
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Débora B
authors.initials: DB
authors.lastname: Tomaz
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Maria Augusta B
authors.initials: MA
authors.lastname: dos Santos
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Anelise S
authors.initials: AS
authors.lastname: Carlessi
authors.affiliation: Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Beatriz I
authors.initials: BI
authors.lastname: Matias
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Laboratório de Biologia Celular e Molecular, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Leffa
authors.affiliation: Laboratório de Biologia Celular e Molecular, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Adriani P
authors.initials: AP
authors.lastname: Damiani
authors.affiliation: Departamento de Engenharia de Biossistemas, Universidade Federal de São João del Rei, São João del Rei, MG, Brazil.
authors.forename: Vitor de C
authors.initials: Vde C
authors.lastname: Gomes
authors.affiliation: Laboratório de Biologia Celular e Molecular, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Andrade
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Departamento de Psicologia, PUC-Rio, Rio de Janeiro, RJ, Brazil.
authors.forename: Jesus
authors.initials: J
authors.lastname: Landeira-Fernadez
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D016194:Receptors, N-Methyl-D-Aspartate; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid
keywords: Anxiety; DNA damage; Depression; Glutamatergic system; Stress