Long-Lasting Hippocampal Synaptic Protein Loss in a Mouse Model of Posttraumatic Stress Disorder

• Published in: PloS one Vol. 7; no. 8; p. e42603
• Main Authors: Herrmann, Leonie, Ionescu, Irina A., Henes, Kathrin, Golub, Yulia, Wang, Nancy Xin Ru, Buell, Dominik R., Holsboer, Florian, Wotjak, Carsten T., Schmidt, Ulrike
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antidepressive Agents, Second-Generation - administration & dosage; Antidepressive Agents, Second-Generation - pharmacology; Anxiety; Apoptosis; Arousal; Biology; Brain; Carrier Proteins - metabolism; Comparative analysis; Complications; Conditioning; Cyclin-dependent kinases; Exposure; Fear; Fear conditioning; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - pharmacology; Footshock; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Homer Scaffolding Proteins; In vivo methods and tests; Male; Medical research; Medicine; Mice; Mice, Inbred C57BL; Models, Animal; Nerve Tissue Proteins - metabolism; Nervous system; Neurogenesis; NMR; Nuclear magnetic resonance; Pathogenesis; Patients; Post traumatic stress disorder; Posttraumatic stress disorder; Proteins; Psychiatry; Rodents; Selective serotonin reuptake inhibitors; Serotonin; Serotonin uptake inhibitors; Shrinkage; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - pathology; Stresses; Studies; Synapsins - metabolism; Synaptophysin - metabolism; Trauma; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042603

Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups. To our knowledge, this is the first systematic in vivo study analyzing the long-term neuromolecular sequelae of acute traumatic stress combined with re-exposure. We show here that a PTSD-like syndrome in mice is accompanied by a long-lasting reduction of hippocampal synaptic proteins which interestingly correlates with the strength of the generalized and conditioned fear response but not with the intensity of hyperarousal symptoms. Furthermore, we demonstrate that treatment with the serotonin reuptake inhibitor (SSRI) fluoxetine is able to counteract both the PTSD-like syndrome and the posttraumatic synaptic protein loss. Taken together, this study demonstrates for the first time that a loss of hippocampal synaptic proteins is associated with a PTSD-like syndrome in mice. Further studies will have to reveal whether these findings are transferable to PTSD patients.