Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder

J Psychiatr Res. 2011 May;45(5):650-9. doi: 10.1016/j.jpsychires.2010.10.014. Epub 2010 Nov 23.

Abstract

Some, but not all studies in patients with posttraumatic stress disorder (PTSD), report reduced hippocampus (HPC) volume. In particular it is unclear, whether smaller hippocampal volume represents a susceptibility factor for PTSD rather than a consequence of the trauma. To gain insight into the relationship of brain morphology and trauma exposure, we investigated volumetric and molecular changes of the HPC in a mouse model of PTSD by means of in vivo Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and ex vivo ultramicroscopic measurements. Exposure to a brief inescapable foot shock led to a volume reduction in both left HPC and right central amygdala two months later. This volume loss was mirrored by a down-regulation of growth-associated protein-43 (GAP43) in the HPC. Enriched housing decreased the intensity of trauma-associated contextual fear, independently of whether it was provided before or after the shock. Beyond that, enriched housing led to an increase in intracranial volume, including the lateral ventricles and the hippocampus, and to an up-regulation of GAP43 as revealed by MEMRI and Western blot analysis, thus partially compensating for trauma-related HPC volume loss and down-regulation of GAP43 expression. Together these data demonstrate that traumatic experience in mice causes a reduction in HPC and central amygdala volume possibly due to a shrinkage of axonal protrusions. Enriched housing might induce trophic changes, which may contribute to the amelioration of trauma-associated PTSD-like symptoms at behavioural, morphological and molecular levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Environment
  • Fear / physiology
  • GAP-43 Protein / metabolism
  • Gene Expression Regulation / physiology
  • Hippocampus / pathology*
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods
  • Male
  • Manganese
  • Mice
  • Mice, Inbred C57BL
  • Reflex / physiology
  • Stress Disorders, Post-Traumatic / pathology*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress Disorders, Post-Traumatic / rehabilitation
  • Time Factors

Substances

  • GAP-43 Protein
  • Manganese