New neurons restore structural and behavioral abnormalities in a rat model of PTSD

Hippocampus. 2019 Sep;29(9):848-861. doi: 10.1002/hipo.23087. Epub 2019 Mar 13.


Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hr produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, 1 month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 region of the hippocampus paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hr daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

Keywords: GFAP-TK; adult neurogenesis; chronic stress; contextual fear conditioning; corticosterone; elevated plus maze; hippocampal volume; neophagia; novelty-suppressed feeding; object place test; single-prolonged stress.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Anxiety / physiopathology
  • Anxiety / psychology
  • Behavior, Animal*
  • CA1 Region, Hippocampal / physiopathology
  • Cell Proliferation
  • Corticosterone / blood
  • Dentate Gyrus / physiopathology
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / physiopathology
  • Male
  • Mice, Transgenic
  • Neurogenesis / drug effects
  • Neurons*
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Restraint, Physical
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Stress Disorders, Post-Traumatic / psychology*
  • Stress, Psychological


  • Glial Fibrillary Acidic Protein
  • glial fibrillary astrocytic protein, mouse
  • Protein-Tyrosine Kinases
  • Corticosterone