Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder

Wen,Yu; Li,Bin; Han,Fang; Wang,Enhua; Shi,Yuxiu

doi:10.3892/mmr.2012.1022

Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder

Authors:
- Yu Wen
- Bin Li
- Fang Han
- Enhua Wang
- Yuxiu Shi
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Affiliations: Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, Shenyang, Liaoning 110001, P.R. China , Department of Orthopaedic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: August 7, 2012 https://doi.org/10.3892/mmr.2012.1022
Pages: 1140-1144

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Abstract

Post-traumatic stress disorder (PTSD) is a significant problem that may affect individuals who have been exposed to a traumatic event or events, including combat, violent crime or childhood abuse. The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment, particularly introspection, amygdala inhibition and emotional memory. In the acute phase of severe traumatic stress, the mPFC appears to undergo a change in plasticity for a short time, which suggests that the mPFC may be the reponse-sensitizing region. Calcium (Ca2+) is one of most significant intracellular messengers; the appropriate concentration of Ca2+ is necessary for neuronal excitability. When the Ca2+ concentration increases, Ca2+, calmodulin (CaM) and CaM kinase IIα (CaMKIIα) combine together to form the Ca2+‑CaM‑CaMKIIα signaling pathway, which is important in the plasticity of the central nervous system, learning and memory, mind, behavior and other types of cognitive activities. Our team studied the changes in the Ca2+-CaM-CaMKIIα levels in the mPFC of rats following a single-prolonged stress (SPS). The SPS, a credible method for establishing a rat model of PTSD, has been internationally recognized. The free intracellular Ca2+ concentration in the mPFC in the PTSD group was significantly higher than that in the control group 1 day after SPS exposure (P<0.05) and decreased 7 days after SPS; CaM expression significantly increased, while CaMKIIα expression significantly decreased in the mPFC 1 day after SPS compared with the control group. These findings suggest dysfunction of the Ca2+-CaM-CaMKIIα cascades in the mPFC, which may relate to the pathogenesis of the abnormal functioning of the mPFC in PTSD.

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