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BMC Psychiatry
Published in: BMC Psychiatry 1/2012

Open Access 01-12-2012 | Research article

Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder

Authors: Dongjuan Liu, Bing Xiao, Fang Han, Enhua Wang, Yuxiu Shi

Published in: BMC Psychiatry | Issue 1/2012

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Abstract

Introduction

Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS). The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter.

Methods

In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM). Levels of Cytochrome c (Cyt-C) was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM). The change of thiamine monophosphatase (TMP) levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM.

Results

Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS.

Conclusions

The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated with PTSD.
Appendix
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Literature
1.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV. 1994, Washington, DC: American Psychiatric Press
2.
Li S, Murakami Y, Wang M, Maeda K, Matsumoto K: The effects of chronic valproate and diazepam in a mouse model of posttraumatic stress disorder. Pharmacol Biochem Behav. 2006, 85 (2): 324-331. 10.1016/j.pbb.2006.08.015.CrossRefPubMed
3.
Siegmund A, Wotjak CT: A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitised fear. J Psychiatr Res. 2007, 41 (10): 848-860. 10.1016/j.jpsychires.2006.07.017.CrossRefPubMed
4.
Kessler RC: Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000, 61 (suppl 5): 4-12.PubMed
5.
Yehuda R, Golier JA, Halligan SL, Meaney M, Bierer LM: The ACTH response to Dexamethasone in PTSD. Am J Psychiatry. 2004, 161 (8): 397-1403.CrossRef
6.
de Kloet CS, Vermetten E, Geuze E, Kavelaars A, Heijnen CJ, Westenberg HG: Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. J Psychiatr Res. 2006, 40 (6): 550-567. 10.1016/j.jpsychires.2005.08.002.CrossRefPubMed
7.
Carrion VG, Weems CF, Watson C, Eliez S, Menon V, Reiss AL: Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res Neuroimaging. 2009, 172 (3): 226-234. 10.1016/j.pscychresns.2008.07.008.CrossRefPubMed
8.
O'Hearn E, Molliver ME: Organization of raphe-cortical projections in rat: a quantitative retrograde study. Brain Res Bull. 1984, 13: 709-726. 10.1016/0361-9230(84)90232-6.CrossRefPubMed
9.
MorinL P, Meyer-Bernstein EL: The ascending serotonergic system in the hamster: comparison with projections of the dorsal and median raphe nuclei. Neuroscience. 1999, 91: 81-105. 10.1016/S0306-4522(98)00585-5.CrossRef
10.
Luo FF, Han F, Shi YX: Change in 5-HT1A receptor in the dorsal raphe nucleus in a rat model of post-traumatic stress disorder. Mol Med Rep. 2011, 4: 843-847.PubMed
11.
Roulston A, Marcellus RC, Branton PE: Virus and apoptosis. Annu Rev Microbiol. 1999, 53: 577-628. 10.1146/annurev.micro.53.1.577.CrossRefPubMed
12.
13.
Peter ME, Krammer PH: The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ. 2003, 10 (1): 26-35. 10.1038/sj.cdd.4401186.CrossRefPubMed
14.
Bantseev V, Youn HY: Mitochondrial “movement” and lens optics following oxidative stress from UV-B irradiation: cultured bovine lenses and human retinal pigment epithelial cells (ARPE-19) as examples. Ann N Y Acad Sci. 2006, 1091: 17-33. 10.1196/annals.1378.051.CrossRefPubMed
15.
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X: Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997, 91: 479-489. 10.1016/S0092-8674(00)80434-1.CrossRefPubMed
16.
Liu X, Kim C, Yang J, Jemmerson R, Wang X: Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996, 86 (1): 147-157. 10.1016/S0092-8674(00)80085-9.CrossRefPubMed
17.
Doty SB, Smith CE, Hand AR, Oliver C: Inorganic trimetaphosphatase as a histochemical marker for lysosomes in light and electron microscopy. J Histochem Cytochem. 1977, 25: 1381-1384. 10.1177/25.12.200672.CrossRefPubMed
18.
Sheen VL, Macklis JD: Apoptotic mechanisms in targeted neuronal cell ddeach by chromophore-activated photolysis. Exp Neurol. 1994, 130 (1): 67-81. 10.1006/exnr.1994.1186.CrossRefPubMed
19.
Iwamoto Y, Morinobu S, Takahashi T, Yamawaki S: Single prolonged stress increases contextual freezing and the expression of glycine transporter 1 and vesicle-associated membrane protein 2 mRNA in the hippocampus of rats. Prog Neuropsychopharmacol Biol Psychiatry. 2007, 31 (3): 642-651. 10.1016/j.pnpbp.2006.12.010.CrossRefPubMed
20.
The Minixtry of Science and Technology of the People’s Republic of China: Guidance Suggestions for the Care and Use of Labortory Animals. 2006
21.
Takahashi T, Morinobu S, Iwamoto Y, Yamawaki S: Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats. Psychopharmacology (Berl). 2006, 189 (2): 165-173. 10.1007/s00213-006-0545-6.CrossRef
22.
Kohda K, Harada K, Kato K, Hoshino A, Motohashi J, Yamaji T, Morinobu S, Matsuoka N, Kato N: Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model. Neuroscience. 2007, 148 (1): 22-33. 10.1016/j.neuroscience.2007.05.041.CrossRefPubMed
23.
Yamamoto S, Morinobu S, Takei S, Fuchikami M, Matsuki A, Yamawaki S, Liberzon I, et al: Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depress Anxiety. 2009, 26: 1110-1117. 10.1002/da.20629.CrossRefPubMed
24.
Liu HY: Technical operations and its common problems of perfusion fixation in mice. Qiqihaer Yixueyuan Xuebao. 2006, 27 (11): 1341-
25.
Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates. 1998, Fourth Edition: Academic Press
26.
Liberzon I, Krstov M, Young EA: Stress–restress: effects on ACTH and fast feedback. Psychoneuroendocrino. 1997, 22: 443-453. 10.1016/S0306-4530(97)00044-9.CrossRef
27.
Imanaka A, Morinobu S, Toki S, Yamawaki S: Importance of early environment in the development of post-traumatic stress disorder-like behaviors. Behav Brain Res. 2006, 173 (1): 129-137. 10.1016/j.bbr.2006.06.012.CrossRefPubMed
28.
Yan Q, Liu JP, Li DW: Apoptosis in lens development and pathology. Differentiation. 2006, 74 (5): 195-211. 10.1111/j.1432-0436.2006.00068.x.CrossRefPubMed
29.
Thomp son CB: Apoptosis in the pathogenesis and treatment of diseade. Science. 1995, 267: 1452-
30.
Finkel E: The mitochondrion: is it central to apoptosis?. Science. 2001, 292 (5517): 624-626. 10.1126/science.292.5517.624.CrossRefPubMed
31.
Brenner C, Kroemer G: Apoptosis: mitochondria-the death signal integrators. Science. 2000, 289 (5482): 1150-1151. 10.1126/science.289.5482.1150.CrossRefPubMed
32.
Tamilselvan J, Jayaraman G, Sivarajan K, Panneerselvam C: Ags-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid. Free Radic Biol Med. 2007, 43 (12): 1656-1669. 10.1016/j.freeradbiomed.2007.08.028.CrossRefPubMed
33.
Latta M, Künstle G, Leist M, Wendel A: Metabolic depletion of ATP by fructose inversely controls CD95- and tumor necrosis factor receptor1-mediated hepatic apoptosis. J Exp Med. 2000, 191 (11): 1975-1985. 10.1084/jem.191.11.1975.CrossRefPubMedPubMedCentral
Metadata
Title
Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder
Authors
Dongjuan Liu
Bing Xiao
Fang Han
Enhua Wang
Yuxiu Shi
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2012
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-12-211

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