The Effect of Obstatin on Stress, Anxiety, Necrosis Cell Death and Apoptosis in the Hippocampus Area in the Model of Fetal Alcohol Spectrum Disorders in Male Rats

Authors

  • Azadeh Toosi1 1- Dept. of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran. orcid http://orcid.org/0000-0002-9227-0627
  • Hooman Shajiee2 2- Dept. of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
  • Mehdi Khaksari3* 3- Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. orcid http://orcid.org/0000-0002-2240-1521
  • Vida Hojati4 4- Dept. of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
  • Golamhassan Vaezi5 5- Dept. of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

DOI:

https://doi.org/10.22100/jkh.v14i4.2310

Keywords:

Obstatin, Ethanol, Anxiety, Necrosis cell death

Abstract

Introduction: Among the numerous consequences of prenatal alcohol exposure (PAE) is an increase in anxiety-like behavior that can prove debilitating to daily functioning. Clinical and experimental evidence has shown postnatal alcohol exposure causes inflammation in the hippocampus and reduced neurogenesis among other brain regions. This can occur during early growth due to the low levels of antioxidants in the brain can be harmful and dangerous. Obstatin is a newly discovered peptide with anti-inflammatory, antioxidant activity, in various animal models.

Methods: Through intragastric intubation, ethanol (5.27 g/kg/day) was administered in male Wistar rat pups on postnatal days 2-10 (third trimester in humans). The animals received obestatin (1 and 5 µg/kg, S.C.) on postnatal days 2-10. Thirty-six days after birth, the anexity test was performed using elevated plus maze test, and then. The level of necrotic and apoptosis cells death was determined via nissl and TUNEL staining after the behavioral test.

Results: Obestatin significantly improved anxiety behavioral deficits (P<0.01), and obestatin treatment could significantly and decreased nissl and tunnel positive cells in the hippocampus of ethanol-exposed rat pups (P<0.01).

Conclusion: The result of this study shows that abstatin had a protective effect on neurodegenerative, alcohol-related behaviors, although further research is needed in the future.

References

Ahlgren SC, Thakur V, Bronner-Fraser M. Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proc Natl Acad Sci USA 2002;99:10476-81. doi: 10.1073/pnas.162356199

Akers KG, Kushner SA, Leslie AT, Clarke L, Van Der Kooy D, Lerch JP, et al. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice. Mol Brain 2011;4:29.doi: 10.1186/1756-6606-4-29

Alfonso-Loeches S, Ureña-Peralta JR, Morillo-Bargues MJ, Guerri C. Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Frontiers in Cellular Neuroscience 2014;8:216. doi: 10.3389/fncel.2014.00216

Alloatti G, Arnoletti E, Bassino E, Penna C, Perrelli MG, GHÉ C, et al. Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes. American Journal of Physiology-Heart and Circulatory Physiology 2010;299:H470-81. doi:10.1152/ajpheart.00800.2009

Andrieu-Abadie N, Gouazé V, Salvayre R, Levade T. Ceramide in apoptosis signaling: relationship with oxidative stress. Free Radical Biology and Medicine 2001;31:717-28. doi: 10.1016/S0891-5849(01)00655-4

Anthony B, Vinci-Booher S, Wetherill L, Ward R, Goodlett C, Zhou FC. Alcohol-induced facial dysmorphology in C57BL/6 mouse models of fetal alcohol spectrum disorder. Alcohol 2010;44:659-71. doi: 10.1016/j.alcohol.2010.04.002

Antonio AM, Gillespie RA, Druse-Manteuffel MJ. Effects of lipoic acid on antiapoptotic genes in control and ethanol-treated fetal rhombencephalic neurons. Brain Res 2011;1383:13-21. doi: 10.1016/j.brainres.2011.01.113

Arenzana FJ, Carvan MJ, Aijon J, Sanchez-Gonzalez R, Arevalo R, Porteros A. Teratogenic effects of ethanol exposure on zebrafish visual system development. Neurotoxicol Teratol 2006;28:342-8. doi: 10.1016/j.ntt.2006.02.001

Arrant AE, Schramm-Sapyta NL, Kuhn CM. Use of the light/dark test for anxiety in adult and adolescent male rats. Behav. Brain Res 2013;256:119-27. doi: 10.1016/j.bbr.2013.05.035

Barak AJ, Beckenhauer HC, Junnila M, Tuma DJ. Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res 1993;17:552-5. doi: 10.1111/j.1530-0277.1993.tb00798.x

Boehm SL, Moore EM, Walsh CD, Gross CD, Cavelli AM, Gigante E, et al. Using drinking in the dark to model prenatal binge-like exposure to ethanol in C57BL/6J mice. Dev Psychobiol 2008;50:566-78. doi: 10.1002/dev 20320

Byrnes EM. Transgenerational consequences of adolescent morphine exposure in female rats: effects on anxiety-like behaviors and morphine sensitization in adult offspring. Psychopharmacology (Berl) 2005;182:537-44. doi:10.1016/j.bbr.2010.11.059

Carneiro LM, Diogenes JP, Vasconcelos SM, Aragao GF, Noronha EC, Gomes PB, et al. Behavioral and neurochemical effects on rat offspring after prenatal exposure to ethanol. Neurotoxicol Teratol 2005;27:585-92. doi:10.1016/j.ntt.2005.06.006

Hellemans KG, Verma P, Yoon E, Yu WK, Young AH, Weinberg Jm. Prenatal alcohol exposure and chronic mild stressdifferentially alter depressive- and anxiety-like behaviors in male and female offspring. Alcohol. Clin Exp Res 2010;34:633-45. doi: 10.1111/j.1530-0277.2009.01132.x

Hofmann CE, Patyk IA, Weinberg J. Prenatal ethanol exposure: sex differences in anxiety and anxiolytic response to a 5-HT1A agonist. Pharmacol Biochem Behav 2005;82:549-58. doi:10.1016/j.pbb.2005.10.010

Holmes A, Parmigiani S, Ferrari PF, Palanza P, Rodgers RJ. Behavioral profile of wild mice in the elevated plus maze test for anxiety. Physiol Behav 2000;71:509-16. doi: 10.1016/S0031-9384(00)00373-5

Hosseinzadeh H, Karimi GR, Rakhshanizadeh M. Anticonvulsant effects of aqueous and ethanolic extracts of hypericum perforatum L in mice. J Med Plant 2004;3:4-6.[Persian].

Hunsberger J, Duman C. Animal models for depression-like and anxiety-like behavior. Protoc Exch 2007; doi:10.1038/nprot.2007.542

Hypericum Perforatum on fear behavior in presence pentylenetetrazole (PTZ) in adult male rat. Ilam Univ Med Sci 2009; 17:36-46.[Persian].

Kastenberger I, Lutsch C, Herzog H, Schwarzer C. Influence of sex genetic background on anxiety-related and stress-induced behavior of prodynorphin deficient mice. PLoS One 2012;7:e34251. doi: 10.1371/journal.pone.0034251

Leach G, Adidharma W, Yan L. Depression- like responses induced by daytime light deficiency in the diurnal grass rat (arvicanthis niloticus). Plos One 2013;8:e57115. doi:10.1371/journal.pone.0057115

Sanchez Vega MC, Chong S, Burne TH. Early gestational exposure to moderate concentrations of ethanol alters adult behaviour in C57BL/6J mice. Behav. Brain Res 2013;252:326-33. doi: 10.1016/j.bbr.2013.06.003

Simon AB, Gorman JM. Advances in the treatment of anxiety: targeting glutamate. Neuro Rx 2006;3:57-68. doi:10.1016/j.nurx.2005.12.005

Smagin DA, Kudryavtseva NN. Anxiogenic and anxiolytic effects of lithium chloride under preventive and therapeutic treatments of male mice /with repeated experience of aggression. Zh Vyssh Nerv Deiat Im I P Pavlova 2014;64:646-59. doi: 10.7868/S0044467714060124

Soetens E, Casaer SD, Hooge R, Hueting JE. Effect of amphetamine on long-term retention of verbal material. Psychopharmacology 1995;119:155-62. doi:10.1007/BF02246156

Sulik KK, Johnston MC, Webb MA. Fetal alcohol syndrome: Embryogenesis in a mouse model. Science 1981;214:936-8. doi:10.1126/science.6795717

Takashi O, Hiroshi S, Ken-ichi M, Katsunori I, Michihiro F, Hiroyuki T, et al. Akihisa treatment: effect on behaviour and neurogenesis in a chronic stress model in mice. BMC Complement Altern Med 2011;11:7.

Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007;2:322-8.9. doi: 10.1096/fj.04-1815fje

Naghdi Badi HA, Amin GH, Makkizadeh M, Ziai SA. St. John's wort (Hypericum perforatum). a review. J Plant Med 2005;4:1-14. [Persian].

Nater UM, Okere U, Stallkamp R, Moor C, Ehlert U, Kliegel M. Psychosocial stress benhances time- based prospective memory in healthy young men. Neurobiology o Learning and Memory 2006;86: 344-8. doi:10.1016/j.nlm.2006.04.006

Ookawa K, Mochizuki K, Shida E, Suzuki T, Suzuki T, Ooba T, et al. Anti-anxiety effect of ovary lipid extracted from Skipjack tuna (Katsuwonus pelamis) in rats. J Vet Med Sci 2007;69:633-6. doi:10.1292/jvms.69.593

Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated Plus maze: a novel test of anxiety in rat. Pharmacol Biochem Behav 1986;24:525-9. doi:10.1016/0091-3057(86)90552-6

Pinheiro SH, Zangrossi H Jr, Del-Ben CM, Graeff FG. Elevated mazes as animal models of anxiety: effects of serotonergic agents. An Acad Bras Cienc 2007;79:71-85. doi: 10.1590/S0001-37652007000100010

Russell KH, Hagenmeyer-Houser SH, Sanberg PR. Haloperidol-induced emotional defecation: a possible model for neuroleptic anxiety syndrome. Psychopharmacology (Berl) 1987;91:45-9. doi: 10.1007/BF00690925

Saleem S, Ahmad M, Ahmad AS, Yousuf S, Ansari MA, Khan MB, et al. Effect of saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats. J Med Food 2006;9:246-53. doi: 10.1089/jmf.2006.9.246

Published

2020-03-17

Issue

Section

Original Article(s)

How to Cite

The Effect of Obstatin on Stress, Anxiety, Necrosis Cell Death and Apoptosis in the Hippocampus Area in the Model of Fetal Alcohol Spectrum Disorders in Male Rats. (2020). Knowledge and Health in Basic Medical Sciences, 14(4), Page:30-39. https://doi.org/10.22100/jkh.v14i4.2310