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.