Effects of calcium-dependent molecular chaperones and endoplasmic reticulum in the amygdala in rats under single‑prolonged stress

Xiao,Bing; Wang,Jian‑Gang; Han,Fang; Shi,Yu‑Xiu

doi:10.3892/mmr.2017.7976

Effects of calcium-dependent molecular chaperones and endoplasmic reticulum in the amygdala in rats under single‑prolonged stress

Authors:
- Bing Xiao
- Jian‑Gang Wang
- Fang Han
- Yu‑Xiu Shi
View Affiliations

Affiliations: Department of Histology and Embryology, Basic Medical Sciences College, China Medical University, Shenyang, Liaoning 110122, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/mmr.2017.7976
Pages: 1099-1104

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The purpose of the present study was to investigate the role of endoplasmic reticulum (ER)‑resident molecular chaperone proteins to identify whether these proteins were involved in post‑traumatic stress disorder (PTSD). The present study detected changes of calreticulin (CRT), calnexin (CNX) and ERp57 in the amygdala of rats, which may with aim of providing a novel insight into the modulation effect of amygdala in PTSD. Single‑prolonged stress (SPS) was applied to create the models of PTSD in rats. The expression levels of CRT, CNX and ERp57 were examined using immunohistochemistry or immunofluorescence, western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The results showed that SPS induced significant changes in CRT, CNX and ERp57 expression levels. Furthermore, the expression levels of CRT, CNX and ERp57 were significantly upregulated when compared to that in the control group after SPS exposure by western blot analysis (P<0.05). RT‑qPCR analysis supported these results, indicating an upregulation of mRNA expression level. Taken together, the present findings suggest that SPS may induce changes to the expression of CRT, CNX and ERp57 in the amygdala of rats. The present study provides an insight into the effects of ER‑resident molecular chaperones in the amygdala participating in PTSD, and provides the experimental basis and a mechanism for the pathophysiology of PTSD.

View Figures

View References

1	American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 5th edition. Arlington, VA: American Psychiatric Publishing; pp. 271–280. 2013
2	Mol SS, Arntz A, Metsemakers JF, Dinant GJ, Vilters-van Monfort PA and Knottnerus JA: Symptoms of post-traumatic stress disorder after non-traumatic events: Evidence from an open population study. Br J Psychiatry. 186:494–499. 2005. View Article : Google Scholar : PubMed/NCBI
3	Wen Y, Li B, Han F, Wang E and Shi Y: Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder. Mol Med Rep. 6:1140–1144. 2012. View Article : Google Scholar : PubMed/NCBI
4	Zhao D, Han F and 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. View Article : Google Scholar : PubMed/NCBI
5	Xie J, Han F and Shi Y: The unfolded protein response is triggered in rat neurons of the dorsal raphe nucleus after single-pronged stress. Neurochem Res. 39:741–747. 2014. View Article : Google Scholar : PubMed/NCBI
6	Zhao W, Han F and Shi YX: IRE1α pathway of endoplasmic reticulum stress induces neuronal apoptosis in the locus coeruleus of rats under single prolonged stress. Prog Neuropsychopharmacol Biol Psychiatry. 69:11–18. 2016. View Article : Google Scholar : PubMed/NCBI
7	Groenendyk J and Michalak M: Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 52:381–395. 2005.PubMed/NCBI
8	Breckenridge DG, Germain M, Mathai JP, Nguyen M and Shore GC: Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 22:8608–8618. 2003. View Article : Google Scholar : PubMed/NCBI
9	Xiang J, Gu X, Qian S and Chen Z: Endoplasmic reticulum stress-mediated apoptosis involved in indirect recognition pathway blockade induces long-term heart allograft survival. J Biomed Biotechnol. 2010:7054312010. View Article : Google Scholar : PubMed/NCBI
10	Lv S, Sun EC, Xu QY, Zhang JK and Wu DL: Endoplasmic reticulum stress-mediated autophagy contributes to bluetongue virus infection via the PERK-eIF2α pathway. Biochem Biophys Res Commun. 466:406–412. 2015. View Article : Google Scholar : PubMed/NCBI
11	Rao RV, Hermel E, Castro-Obregon S, del Rio G, Ellerby LM, Ellerby HM and Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem. 276:33869–33874. 2001. View Article : Google Scholar : PubMed/NCBI
12	Boyce M and Yuan J: Cellular response to endoplasmic reticulum stress: A matter of life or death. Cell Death Differ. 13:363–373. 2006. View Article : Google Scholar : PubMed/NCBI
13	Prell T, Lautenschläger J and Grosskreutz J: Calcium-dependent protein folding in amyotrophic lateral sclerosis. Cell Calcium. 54:132–143. 2013. View Article : Google Scholar : PubMed/NCBI
14	Bernales S, Papa FR and Walter P: Intracellular signaling by the unfolded protein response. Annu Rev Cell Dev Biol. 22:487–508. 2006. View Article : Google Scholar : PubMed/NCBI
15	Jung J and Michalak M: Cell surface targeting of myelin oligodendrocyte glycoprotein (MOG) in the absence of endoplasmic reticulum molecular chaperones. Biochim Biophys Acta. 1813:1105–1110. 2011. View Article : Google Scholar : PubMed/NCBI
16	Williams DB: Beyond lectins: The calnexin/calreticulin chaperone system of the endoplasmic reticulum. J Cell Sci. 119:615–623. 2006. View Article : Google Scholar : PubMed/NCBI
17	Hebert DN and Molinari M: In and out of the ER: Protein folding, quality control, degradation, and related human diseases. Physiol Rev. 87:1377–1408. 2007. View Article : Google Scholar : PubMed/NCBI
18	Itakura M, Tsujimura J, Yamamori S, Ohkido T and Takahashi M: NMDA receptor-dependent recruitment of calnexin to the neuronal plasma membrane. Neurosci Lett. 550:173–178. 2013. View Article : Google Scholar : PubMed/NCBI
19	Ellgaard L, Riek R, Herrmann T, Güntert P, Braun D, Helenius A and Wüthrich K: NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA. 98:3133–3138. 2001. View Article : Google Scholar : PubMed/NCBI
20	Coe H and Michalak M: ERp57, a multifunctional endoplasmic reticulum resident oxidoreductase. Int J Biochem Cell Biol. 42:796–799. 2010. View Article : Google Scholar : PubMed/NCBI
21	Ellgaard L and Frickel EM: Calnexin, calreticulin, and ERp57: Teammates in glycoprotein folding. Cell Biochem Biophys. 39:223–247. 2003. View Article : Google Scholar : PubMed/NCBI
22	Szydlowska K and Tymianski M: Calcium, ischemia and excitotoxicity. Cell Calcium. 47:122–129. 2010. View Article : Google Scholar : PubMed/NCBI
23	Amunts K, Kedo O, Kindler M, Pieperhoff P, Mohlberg H, Shah NJ, Habel U, Schneider F and Zilles K: Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: Intersubject variability and probability maps. Anat Embryol (Berl). 210:343–352. 2005. View Article : Google Scholar : PubMed/NCBI
24	Davis M and Whalen PJ: The amygdala: Vigilance and emotion. Mol Psychiatry. 6:13–34. 2001. View Article : Google Scholar : PubMed/NCBI
25	Pape HC: Petrified or aroused with fear: The central amygdala takes the lead. Neuron. 67:527–529. 2010. View Article : Google Scholar : PubMed/NCBI
26	Solano-Castiella E, Anwander A, Lohmann G, Weiss M, Docherty C, Geyer S, Reimer E, Friederici AD and Turner R: Diffusion tensor imaging segments the human amygdala in vivo. Neuroimage. 49:2958–2965. 2010. View Article : Google Scholar : PubMed/NCBI
27	Young MB and Thomas SA: M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current. J Neurosci. 34:1570–1578. 2014. View Article : Google Scholar : PubMed/NCBI
28	Mihaljević S, Vuksan-Ćusa B, Marčinko D, Koić E, Kušević Z and Jakovljević M: Spiritual well-being, cortisol, and suicidality in croatian war veterans suffering from PTSD. J Relig Health. 50:464–473. 2011. View Article : Google Scholar : PubMed/NCBI
29	Yamamoto S, Morinobu S, Takei S, Fuchikami M, Matsuki A, Yamawaki S and Liberzon I: Single prolonged stress: Toward an animal model of posttraumatic stress disorder. Depress Anxiety. 26:1110–1117. 2009. View Article : Google Scholar : PubMed/NCBI
30	Wang W, Liu Y, Zheng H, Wang HN, Jin X, Chen YC, Zheng LN, Luo XX and Tan QR: A modified single-prolonged stress model for post-traumatic stress disorder. Neurosci Lett. 441:237–241. 2008. View Article : Google Scholar : PubMed/NCBI
31	Khan S and Liberzon I: Topiramate attenuated exaggerated acoustic startle in an animal model of PTSD. Psychopharmacology (Berl). 172:225–229. 2004. View Article : Google Scholar : PubMed/NCBI
32	Chavez CM, McGaugh JL and Weinberger NM: The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex. Neurobiol Learn Mem. 91:382–392. 2009. View Article : Google Scholar : PubMed/NCBI
33	Xiao B, Han F and Shi YX: Dysfunction of Ca2+/CaM kinase IIalpha cascades in the amygdala in post-traumatic stress disorder. Int J Mol Med. 24:795–799. 2009.PubMed/NCBI