Single-Prolonged-Stress-Induced Changes in Autophagy-Related Proteins Beclin-1, LC3, and p62 in the Medial Prefrontal Cortex of Rats with Post-traumatic Stress Disorder.
Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis. PTSD was induced in rats by exposure to a single-prolonged stress (SPS). The Morris water maze was used to assess cognitive changes in rats from the SPS and control groups. Transmission electron microscopy (TEM) was employed to observe mPFC morphological changes. Immunohistochemistry, immunofluorescence, and Western blotting techniques were used to detect expression of Beclin-1, LC3, and p62 in the mPFC. The Morris water maze test results showed that the escape latency time was increased and that the percent time in the target quadrant was decreased in the SPS group compared with that in the control group. Numerous visible autolysosomes in mPFC neurons were observed using TEM after SPS stimulation. Compared with that in the control group, the expression of Beclin-1 and the LC3-II/I ratio significantly decreased at 1 day, then increased and peaked at 7 days, and slightly decreased at 14 days after SPS stimulation, whereas the converse was found for p62 expression. In conclusion, dysregulation of autophagic activity in the mPFC may play a crucial role in PTSD pathogenesis.
PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China.|Department of Radiology, First Affiliated Hospital of Jinzhou Medical University, No. 2 fifth Duan, Renmin Street, Jinzhou, Liaoning, 121001, China.
Shilei
S
Zheng
PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China.
Fang
F
Han
PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China. shiyuxiu@163.com.
Yuxiu
Y
Shi
PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China.
Lili
L
Wen
PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China.
Dan
D
Han
D000818:Animals; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018782:Maze Learning; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000071456:Sequestosome-1 Protein / Q000235:genetics / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat
Autophagy; Beclin-1; Medial prefrontal cortex; Microtubule-associated protein 1 light chain 3; Post-traumatic stress disorder; Single-prolonged stress; p62/SQSTM1