Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder.
Among learning and memory processes, fear memories are crucial in some psychiatric disorders like post-traumatic stress disorder (PTSD). Accumulating evidence shows that the sigma-1 receptor (Sig-1R) has comprehensive involvement in cognitive impairment and neuroprotective effects. It has also been reported that BDNF appears to enhance extinction of fear in anxiety disorders via the MAPK signaling cascade. However, it remains unclear whether BDNF-TrkB-MAPK pathway may be mechanistically involved in the therapeutic effect of sigma-1 receptor in the development of PTSD. To address this question, rats were subjected to a classical single-prolonged stress procedure (SPS) and kept undisturbed for 7 days. After that, rats were re-stressed by re-exposure to the forced swim component of SPS (RSPS). Behavior tests were subsequently performed to assess anxiety and cognitive impairments. Furthermore, we analyzed the expression of BDNF and the phosphorylation of TrkB and three MAPK pathways, namely, the ERK, JNK and p38. We found that the levels of BDNF and p-TrkB were increased following the RSPS procedure, which were reversed by the administration of PRE-084. Meanwhile, among the three MAPK signaling pathways, only the p-ERK expression was increased following the RSPS procedure. Collectively, our results indicate that BDNF-TrkB-ERK signaling pathway may be involved in the activation of sigma-1 receptor to yield therapeutic benefits for PTSD.
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
Li-Li
LL
Ji
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
Jun-Bo
JB
Peng
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
Chang-Hai
CH
Fu
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
Dong
D
Cao
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China.
Dan
D
Li
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China. Electronic address: tonglei@mail.cmu.edu.cn.
Lei
L
Tong
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, People's Republic of China. Electronic address: zywang@live.cn.
Zhen-Yu
ZY
Wang
D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000097605:Sigma-1 Receptor
D019208:Brain-Derived Neurotrophic Factor; D009025:Morpholines; D011619:Psychotropic Drugs; D020813:Receptor, trkB; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C000621230:Ntrk2 protein, rat
PRE-084; Post-traumatic stress disorder; Sigma-1 receptor; Single prolonged stress