Involvement of calcineurin/NFATc4 pathway in a single-prolonged stress-based rat model of post-traumatic stress...

Post-traumatic stress disorder (PTSD) is a mental disease associated with the exposure of traumatic stress, and results in the structural and functional changes of hippocampus. Calcineurin (CaN), a calcium/calmodulin-regulated protein phosphatase ubiquitously expressed in brain, has a very important role in the fear extinction, neuronal structure and neuronal excitability. With CaN activation, its down target nuclear factor of activated T cells (NFATs) dephosphorylated and then translocated from the cytoplasm to the nucleus to affect neuronal function, resulting in the function changes of brain structure such as hippocampus. Increasing evidence has suggested that CaN/NFATs signaling are involved in the regulation of mental disorders like Alzheimer's disease, depression, while little is known about its effects on the molecular mechanisms on PTSD. This study seek to know the relationship between PTSD and CaN/NFATc4 pathway, and to detect whether CaN/NFATc4 pathway are involved in the hippocampus dysfunctions in a single-prolonged stress (SPS)-based rat model of PTSD. Our results have showed that after 4 days exposed to SPS, the protein expression of CaN up-regulated and the NFATc4 dephosphorylated and imported into the nucleus; while at the 7 and 14 day exposed to SPS, with the down-regulation of CaN, the expression of phosphorylate-NFATc4 increased. Our results show that CaN/NFATc4 pathway were involved in the development of PTSD model, which suggested that the changes of CaN/NFATc4 pathway may be one of the pathological molecular mechanism in the dysfunction of hippocampus in PTSD.