Long-term down-regulation of BDNF mRNA in rat hippocampal CA1 subregion correlates with PTSD-like behavioural stress response.

Abstract

Brain-derived neurotrophic factor (BDNF) and its intracellular kinase-activating receptor TrkB, have been implicated in the neurobiological mechanisms underlying the clinical manifestations of PTSD, especially those related to synaptic efficacy and neural plasticity. BDNF interacts with components of the stress response such as corticosterone, and plays an important role in growth, maintenance and functioning of several neuronal systems. This study employed an animal model of PTSD to investigate the relationship between prevalence rates of distinct patterns of behavioural responses to predator stress, circulating levels of corticosterone and local levels of mRNA for BDNF, TrkB and two other neurotrophic factors in selected brain areas. Animals whose behaviour was extremely disrupted by exposure selectively displayed significant down-regulation of mRNA for BDNF and up-regulation of TrkB mRNA in the CA1 subregion of the hippocampus, compared to animals whose behaviour was minimally or partially affected and to unexposed controls. The response was consistent throughout the entire study only in CA1. The consistent long-term the BDNF down-regulation and TrkB up-regulation associated with extreme behavioural compromise may be associated with chronic stress-induced psychopathological processes, especially in the hippocampus. The corresponding changes in neural plasticity and synaptic functioning may mediate clinical manifestations of PTSD.

• Authors: Nitsan Kozlovsky, Michael A Matar, Zeev Kaplan, Moshe Kotler, Joseph Zohar, Hagit Cohen
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 10 Issue 6 Pg. 741-58 (Dec 2007) ISSN: 1461-1457 [Print] England
• PMID: 17291374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• DNA Primers
• Neurotrophin 3
• RNA, Messenger
• Nerve Growth Factor
• Receptor, trkB
• Corticosterone

Topics

• Acoustic Stimulation
• Animals
• Anxiety (psychology)
• Behavior, Animal (drug effects)
• Blotting, Western
• Brain Chemistry (drug effects)
• Brain-Derived Neurotrophic Factor (biosynthesis, genetics, physiology)
• Corticosterone (blood)
• DNA Primers
• Down-Regulation (drug effects)
• Hippocampus (drug effects, metabolism)
• Male
• Nerve Growth Factor (metabolism)
• Neuronal Plasticity (drug effects)
• Neurotrophin 3 (metabolism)
• Prefrontal Cortex (drug effects, metabolism)
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Receptor, trkB (metabolism)
• Reflex, Startle (drug effects)
• Stress Disorders, Post-Traumatic (psychology)