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Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder

Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder

Pereira Dias, Gisele ORCID: 0000-0001-7276-2010, Bevilaqua, Mario Cesar do Nascimento, Silveira, Anna Claudia Domingos, Fleming, Renata Lopes, de Carvalho, Litia Alves, Cocks, Graham, Beckman, Danielle, Hosken, Lucas Costa, Corrêa-e-Castro, Ana Carolina, Mousovich-Neto, Felippe, Gomes, Vítor de Castro, Bastos, Gilmara de Nazareth Tavares, Kubrusly, Regina Célia Cussa, da Costa, Vânia Maria Corrêa, Srivastava, Deepak, Landeira-Fernandez, Jesus, Nardi, Antonio Egidio, Thuret, Sandrine and Gardino, Patricia Franca (2014) Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder. Behavioural Brain Research, 263. pp. 34-45. ISSN 0166-4328 (Print), 1872-7549 (Online) (doi:

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Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated animal model for GAD, to identify biomarkers and structural changes in the hippocampus that could be part of the underlying mechanisms of their high-anxiety profile. Spatial and fear memory was assessed in the Morris water maze and passive avoidance test. Serum corticosterone levels, immunofluorescence for glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for hippocampal brain derived neurotrophic factor (BDNF) were performed. Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67), neuroblasts (doublecortin), and cell survival were undertaken in the DG, along with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA release was assessed by neurochemical assay.

Fear memory was higher among CHF rats whilst spatial learning was preserved. Serum corticosterone levels were increased, with decreased GR expression. No differences were observed in hippocampal cell proliferation/survival, but the number of newborn neurons was decreased, along with their number and length of tertiary dendrites. Increased expression of proBDNF and dendritic spines was observed; lower ratio of GABA release in the hippocampus was also verified. These findings suggest that generalized anxiety/fear could be associated with different hippocampal biomarkers, such as increased spine density, possibly as a compensatory mechanism for the decreased hippocampal number of neuroblasts and dendritic arborization triggered by high corticosterone. Disruption of GABAergic signaling and BDNF impairment are also proposed as part of the hippocampal mechanisms possibly underlying the anxious phenotype of this model.

Item Type: Article
Uncontrolled Keywords: Fear memory, Anxiety, Adult hippocampal neurogenesis, BDNF, Dendritic arborisation, Dendritic spines
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Faculty / School / Research Centre / Research Group: Faculty of Education, Health & Human Sciences
Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified: 15 Apr 2020 14:02

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