Distinctive hippocampal and amygdalar cytoarchitectural changes underlie specific patterns of behavioral disruption following stress exposure in an animal model of PTSD

• Published in: European neuropsychopharmacology 2014-12, Vol.24 (12), p.1925-1944
• Main Authors: Cohen, Hagit, Kozlovsky, Nitsan, Matar, Michael A, Zohar, Joseph, Kaplan, Zeev
• Format: Article
• Language: English
• Subjects: Amygdala - metabolism; Amygdala - pathology; Animal model; Animals; Brain-Derived Neurotrophic Factor - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; CREB-Binding Protein - metabolism; Cytoarchitecture; Dendrites - pathology; Dendrites - ultrastructure; Disease Models, Animal; Disks Large Homolog 4 Protein; Hippocampus - metabolism; Hippocampus - pathology; Internal Medicine; Intracellular Signaling Peptides and Proteins - metabolism; Male; Maze Learning; Membrane Proteins - metabolism; Neuronal plasticity; Neurons - pathology; Posttraumatic stress disorder; Psychiatry; Rats; Receptors, AMPA - metabolism; Receptors, Glucocorticoid - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Reflex, Startle; Resilience; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - pathology; Vulnerability
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2014.09.009

Abstract Alterations in cytoarchitecture and molecular signaling have been observed in adaptive and maladaptive responses to stress and presumably underlie the physiological and behavioral changes observed. The relationship between behavioral responses to stress exposure and changes in cytoarchitecture of subregions of the hippocampus and amygdala was investigated in an animal model of PTSD. Behaviors in elevated plus-maze and acoustic startle response tests were assessed in rats 7 days after exposure to predator scent stress. Brains were harvested 24 h later. Neurons from CA1, CA3, and dentate gyrus subregions and basolateral amygdala were reconstructed and subjected to Sholl analysis and spine density estimation. Glucocorticoid receptor, brain-derived neurotrophic factor, phospho-NR1-Ser-889, phospho-GluR1-Ser-845, phospho-calcium/calmodulin dependent protein kinase II-Thy-286, post-synaptic density protein 95 and phospho-CREB-Ser-133 were evaluated in the hippocampus. Data were analyzed by retrospective classification of individual rats into three behavioral response groups. The extent and distribution of changes in the morphology of hippocampal and amygdalar dendrites was significantly associated with stress-induced behavioral response classification. Extreme (PTSD-like) behavioral disruption was associated with extensive neuronal retraction in the hippocampus and proliferation in the amygdala. Neither structure displayed such changes in minimal behavioral responders. Partial behavioral response was associated with identical changes in the hippocampus only. Patterns of change in requisite molecular signaling genes and endophenotypic markers corresponded to the structural and behavioral responses. The extent and distribution of changes in the cytoarchitecture of hippocampal and amygdalar subregions is directly related to the pattern of behavioral response of the individual to stress exposure.