Changes in integrin αv, vinculin and connexin43 in the medial prefrontal cortex in rats under single-prolonged stress

Li,Yana; Han,Fang; Shi,Yuxiu

doi:10.3892/mmr.2014.3030

Changes in integrin αv, vinculin and connexin43 in the medial prefrontal cortex in rats under single-prolonged stress

Authors:
- Yana Li
- Fang Han
- Yuxiu Shi
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Affiliations: Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: December 2, 2014 https://doi.org/10.3892/mmr.2014.3030
Pages: 2520-2526
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Post‑traumatic stress disorder (PTSD) is a stress‑accociated mental disorder that occurs as a result of exposure to a traumatic event, with characteristic symptoms, including intrusive memories, hyperarousal and avoidance. The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment, particularly introspection, inhibition of the amygdala and emotional memory. Previous structural neuroimaging studies have revealed that the mPFC of PTSD patients was significantly smaller when compared with that of controls and their emotional adjustment function was weakened. However, the mechanisms that cause such atrophy remain to be elucidated. The aim of the present study was to elucidate the possible mechanisms involved in apoptosis induced by single‑prolonged stress (SPS) in the mPFC of PTSD rats. SPS is an animal model reflective of PTSD. Of the proposed animal models of PTSD, SPS is one that has been shown to be reliably reproducible in patients with PTSD. Wistar rats were sacrificed at 1, 4, 7 and 14 days after exposure to SPS. Apoptotic cells were assessed using electron microscopy and the TUNEL method. Expression of integrin αv, vinculin and connexin43 were detected using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction. The present results demonstrated that apoptotic cells significantly increased in the mPFC of SPS rats, accompanied with changes in expression of integrin αv, vinculin and connexin43. The present results indicated that SPS‑induced apoptosis in the mPFC of PTSD rats and the mitochondrial pathway were involved in the process of SPS‑induced apoptosis.

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1	Sherin JE and Nemeroff CB: Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues Clin Neurosci. 13:263–278. 2011.PubMed/NCBI
2	Vermetten E: Stress, trauma, and post-traumatic stress disorder. Tijdschr Psychiatr. 51:595–602. 2009.(In Dutch).
3	Liberzon I, Krstov M and Young EA: Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology. 22:443–453. 1997. View Article : Google Scholar : PubMed/NCBI
4	Roozendaal B, Griffith QK, Buranday J, De Quervain DJ and McGaugh JL: The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: dependence on the basolateral amygdala. Proc Natl Acad Sci USA. 100:1328–1333. 2003. View Article : Google Scholar : PubMed/NCBI
5	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.PubMed/NCBI
6	Bremner JD: Neuroimaging studies in post-traumatic stress disorder. Curr Psychiatry Rep. 4:254–263. 2002. View Article : Google Scholar : PubMed/NCBI
7	Rauch SL, Shin LM and Phelps EA: Neurocircuitry models of posttraumafic stress disorder and extinction: human neuroimaging research - past, present, and future. Biol Psychiatry. 60:376–382. 2006. View Article : Google Scholar : PubMed/NCBI
8	Xiao B, Yu B, Wang HT, Han F and Shi YX: Single-prolonged stress induces apoptosis by activating cytochrome C/caspase-9 pathway in a rat model of post-traumatic stress disorder. Cell Mol Neurobiol. 31:37–43. 2011. View Article : Google Scholar
9	Fink G: Stress controversies: post-traumatic stress disorder, hippocampal volume, gastroduodenal ulceration. J Neuroendocrinol. 23:107–117. 2011. View Article : Google Scholar
10	Wang HT, Han F and Shi YX: Activity of the 5-HT1A receptor is involved in the alteration of glucocorticoid receptor in hippocampus and corticotropin-releasing factor in hypothalamus in SPS rats. Int J Mol Med. 24:227–231. 2009.PubMed/NCBI
11	Becchetti A, Pillozzi S, Morini R, Nesti E and Arcangeli A: New insights into the regulation of ion channels by integrins. Int Rev Cell Mol Biol. 279:135–190. 2010. View Article : Google Scholar : PubMed/NCBI
12	Sheppard D: Roles of alphav integrins in vascular biology and pulmonary pathology. Curr Opin Cell Biol. 16:552–557. 2004. View Article : Google Scholar : PubMed/NCBI
13	Chatzizacharias NA, Kouraklis GP and Theocharis SE: The role of focal adhesion kinase in early development. Histol Histopathol. 25:1039–1055. 2010.PubMed/NCBI
14	Khan S and Liberzon I: Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD. Psychopharmacology (Berl). 172:225–229. 2004. View Article : Google Scholar
15	Takahashi T, Morinobu S, Iwamoto Y and Yamawaki S: Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats. Psychopharmacology (Berl). 189:165–173. 2006. View Article : Google Scholar
16	Zhu CZ, Situ MJ, Zhang Y, Fang H, Jing LS, Wang D, Yan J and Huang Y: Influence factors of post-traumatic stress disorder (PTSD) and depression symptoms in children and adolescents after Wenchuan earthquake in China. Zhonghua Yu Fang Yi Xue Za Zhi. 45:531–536. 2011.(In Chinese). PubMed/NCBI
17	Milner R and Campbell IL: The integrin family of cell adhesion molecules has multiple functions within the CNS. J Neurosci Res. 69:286–291. 2002. View Article : Google Scholar : PubMed/NCBI
18	Gold AL, Shin LM, Orr SP, Carson MA, Rauch SL, Macklin ML, Lasko NB, Metzger LJ, Dougherty DD, Alpert NM, Fischman AJ and Pitman RK: Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder. Psychol Med. 13:1–10. 2011.
19	Su TP, Zhang L, Chung MY, Chen YS, Bi YM, Chou YH, Barker JL, Barrett JE, Maric D, Li XX, Li H, Webster MJ, Benedek D, Carlton JR and Ursano R: Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders. J Psychiatr Res. 43:1078–1085. 2009. View Article : Google Scholar : PubMed/NCBI
20	Mierke CT: The role of vinculin in the regulation of the mechanical properties of cells. Cell Biochem Biophys. 53:115–126. 2009. View Article : Google Scholar : PubMed/NCBI
21	Brohawn KH, Offringa R, Pfaff DL, Hughes KC and Shin LM: The neural correlates of emotional memory in posttraumatic stress disorder. Biol Psychiatry. 68:1023–1030. 2010. View Article : Google Scholar : PubMed/NCBI
22	Jordà EG, Verdaguer E, Jimenez A, Arriba SG, Allgaier C, Pallàs M and Camins A: Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis. Biochem Pharmacol. 70:470–480. 2005. View Article : Google Scholar : PubMed/NCBI
23	Gary DS and Mattson MP: Integrin signaling via the PI3-kinase-Akt pathway increases neuronal resistance to glutamate-induced apoptosis. J Neurochem. 76:1485–1496. 2001. View Article : Google Scholar : PubMed/NCBI
24	Demir O, Singh S, Klimaschewski L and Kurnaz IA: From birth till death: neurogenesis, cell cycle, and neurodegeneration. Anat Rec (Hoboken). 292:1953–1961. 2009. View Article : Google Scholar
25	Leerberg JM and Yap AS: Vinculin, cadherin mechanotransduction and homeostasis of cell-cell junctions. Protoplasma. 250:817–829. 2013. View Article : Google Scholar : PubMed/NCBI
26	Klee P and Meda P: Connexin signaling: a new mechanism for protection of insulin-producing cells against apoptosis. Med Sci (Paris). 28:41–44. 2012.(In French). View Article : Google Scholar
27	Nandrot EF, Silva KE, Scelfo C and Finnemann SC: Retinal pigment epithelial cells use a MerTK-dependent mechanism to limit the phagocytic particle binding activity of αvβ5 integrin. Biol Cell. 104:326–341. 2012. View Article : Google Scholar : PubMed/NCBI
28	Kawaguchi SY and Hirano T: Integrin alpha3beta1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron. Mol Cell Neurosci. 31:416–426. 2006. View Article : Google Scholar
29	Farwell AP, Tranter MP and Leonard JL: Thyroxine-dependent regulation of integrin-laminin interactions in astrocytes. Endocrinology. 136:3909–3915. 1995.PubMed/NCBI
30	Mobley AK and McCarty JH: Use of Cre-lox technology to analyze integrin functions in astrocytes. Methods Mol Biol. 814:555–570. 2012. View Article : Google Scholar
31	Carisey A and Ballestrem C: Vinculin, an adapter protein in control of cell adhesion signalling. Eur J Cell Biol. 90:157–163. 2010. View Article : Google Scholar : PubMed/NCBI
32	Li WE and Nagy JI: Connexin43 phosphorylation state and intercellular communication in cultured astrocytes following hypoxia and protein phosphatase inhibition. Eur J Neurosci. 12:2644–2650. 2000. View Article : Google Scholar : PubMed/NCBI
33	Solan JL and Lampe PD: Connexin43 phosphorylation: structural changes and biological effects. Biochem J. 419:261–272. 2009. View Article : Google Scholar : PubMed/NCBI
34	Irie A: Integrin family. Nihon Rinsho. 68:163–166. 2010.(In Japanese).
35	Lv X, Su L, Yin D, Sun C, Zhao J, Zhang S and Miao J: Knockdown of integrin beta4 in primary cultured mouse neurons blocks survival and induces apoptosis by elevating NADPH oxidase activity and reactive oxygen species level. Int J Biochem Cell Biol. 40:689–699. 2008. View Article : Google Scholar