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Effect of Glucose-Regulated Protein 94 and Endoplasmic Reticulum Modulator Caspase-12 in Medial Prefrontal Cortex in a Rat Model of Posttraumatic Stress Disorder

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Abstract

Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by a life-threatening traumatic experience, which affects a patient’s quality of life and social stability. The objective of this study was to investigate the change of the glucose-regulated protein (GRP) 94 and apoptosis-related caspase-12 expression in medial prefrontal cortex (mPFC) in rats to determine whether endoplasmic reticulum apoptosis pathway plays an important role in single-prolonged stress (SPS), a well-established PTSD animal model, and therefore to provide experimental evidence to reveal PTSD pathogenesis. A total of 120 healthy male Wistar rats were selected for this study, randomly divided into a normal control group and SPS groups of 1, 4, 7, 14, and 28 days. Behavioral studies of the learning and memory capabilities of rats were observed by using Morris water maze. Morphological changes were detected using transmission electron microscopy (TEM). Immunohistochemistry, Western blot, and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expressions of caspase-12 and GRP94 expressions in mPFC. Our results showed that compared with control groups, after the SPS exposure, the average escape latency was prolonged in place navigation test (P < 0.05), and swimming time in the third quadrant in spatial probe test shortened. The morphological change of mPFC in each SPS group bears typical apoptotic characteristics. The expressions of GRP94 and caspase-12 gradually increased on 1 and 4 days, peaked on 7 days after the SPS exposure, and then decreased. These results suggest that SPS exposure can induce apoptotic neurons and a change of caspase-12 and GRP94 expression in the mPFC, which may be one of the pathogenesis of mPFC abnormal function in PTSD.

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Acknowledgments

This research was supported by grants from the National Natural Science Foundation of China (No. 81171282; No. 31200772) and research fund from the doctoral program of High Education of China (No. 20132104110021). The authors would like to thank the reviewers for their valuable comments on how to improve the quality of the paper.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 92 Beima Road, Heping District, Shenyang, 110001, Liaoning Province, China

    Dongmei Zhao, Fang Han & Yuxiu Shi

  2. Department of Human Anatomy, Binzhou Medical University, Yantai, 264003, Shandong Province, China

    Dongmei Zhao

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  1. Dongmei Zhao
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  2. Fang Han
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  3. Yuxiu Shi
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Correspondence to Yuxiu Shi.

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Zhao, D., Han, F. & Shi, Y. Effect of Glucose-Regulated Protein 94 and Endoplasmic Reticulum Modulator Caspase-12 in Medial Prefrontal Cortex in a Rat Model of Posttraumatic Stress Disorder. J Mol Neurosci 54, 147–155 (2014). https://doi.org/10.1007/s12031-014-0263-1

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  • DOI: https://doi.org/10.1007/s12031-014-0263-1

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