Medroxyprogesterone acetate improves propionic acid-induced autism rat model and magnetic resonance spectroscopic correlation

Authors

DOI:

https://doi.org/10.3329/bjp.v17i2.59412

Keywords:

Autism; Medroxyprogesterone acetate; Propionic acid; GFAP; Rat; MR spectroscopy

Abstract

The protective effect of medroxyprogesterone acetate on propionic acid-induced autism in rats was evaluated. For this purpose, 30 rats were divided into three groups. The significant difference in the levels of IL-17 (p<0.05), IL-2 (p<0.05), and TNF-α (p<0.05), lactate (p<0.05), and nerve growth factor (p<0.05) were found in the medroxyprogesterone-treated group by biochemical analysis. In histopathological examination, the medroxyprogesterone-treated group revealed significant improvement in neural body degeneration, neural count, and dysmorphological changes in both CA1 and CA3 regions. Immunohistochemical examination revealed improvement in glial activity with glial fibrillar acidic protein and morphological changes in Purkinje cells. Magnetic resonance spectroscopy showed an improvement in the level of lactate duplets in the medroxyprogesterone-treated group. To our knowledge, this is the first study, to evaluate the protective effect of medroxyprogesterone on propionic acid-induced autism in rats.

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Author Biography

Oytun Erbaş, Department of Physiology, Cephalink Institute, Demiroğlu Bilim University, Gebze, Turkey.

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References

Al-Amin MM, Rahman MM, Khan FR, Zaman F, Mahmud Reza H. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism. Behav Brain Res. 2015; 286: 112-21.

Al-Dbass AM. N-Acetylcysteine reduces the neurotoxic effects of propionic acid in rat pups. J King Saud Univ Sci. 2014; 26: 254-60.

Al-Gholam MA, Ameen O. The neuroprotective effect of Ginkgo Biloba extract on valproic acid induced autistic features in mice. J Clin Diagnostic Res. 2020; 1-7.

Arafat EA, Shabaan DA. The possible neuroprotective role of grape seed extract on the histopathological changes of the cerebellar cortex of rats prenatally exposed to valproic acid: Animal model of autism. Acta Histochem. 2019; 121: 841-51.

Bakshi V, Sunand K, Begum N, Kakalij RM, Tekula MR. Neuroprotective effect of resveratrol on valproic acid induced oxidative stress autism in Swiss albino mice. Int J Pharm Sci Drug Res. 2018; 10:103-10.

Bambini-Junior V, Rodrigues L, Behr GA, Moreira JCF, Riesgo R, Gottfried C. Animal model of autism induced by prenatal exposure to valproate: Behavioral changes and liver parameters. Brain Res. 2011; 1408: 8-16.

Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: A review and future directions. Int J Dev Neurosci. 2005; 23: 183-87.

Bentel JM, Birrell SN, Pickering MA, Holds DJ, Horsfall DJ, Tilley WD. Androgen receptor agonist activity of the syn-thetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol. 1999; 154: 11-20.

Bill BR, Geschwind DH. Genetic advances in autism: Heterogeneity and convergence on shared pathways. Curr Opin Genet Dev. 2009; 19: 271-78.

Braun JM. Endocrine disrupting compounds, gonadal hormones, and autism. Dev Med Child Neurol. 2012; 54: 1068-68.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-54.

Celik I, Seker M, Salbacak A. Histological and histomorphometric studies on the cerebellar cortex and silver stained nucleolus organizer regions of Purkinje neurons in chronic morphine-treated rats. Vet Arh. 2018; 88: 75-88.

Correia C, Coutinho AM, Diogo L, Grazina M, Marques C, Miguel T, Ataíde A, Almeida J, Borges L, Oliveira C, Oliveira G, Vicente AM. Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: No association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene. J Autism Dev Disord. 2006; 36:1137-40.

Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J. Mapping early brain development in autism. Neuron. 2007; 224.

Dringen R. Oxidative and antioxidative potential of brain microglial cells. Antioxid Redox Signal. 2005; 74: 374-80.

El-Eraky El-Azab N, M. El-Mahalaway A, Sabry D. Effect of methyl mercury on the cerebellar cortex of rats and the possible neuroprotective role of mesenchymal stem cells conditioned medium: Histological and immunohistochemical study. J Gastrointest Cancer Stromal Tumors. 2018; 8: 2.

Erbas O, Erdogan MA, Khalilnezhad A, Gürkan FT, Yiğittürk G, Meral A, Taskiran D. Neurobehavioral effects of long-term maternal fructose intake in rat offspring. Int J Dev Neurosci. 2018; 69: 68-79.

Erbaş O, Solmaz V, Aksoy D, Yavaşoǧlu A, Saǧcan M, Taşkiran D. Cholecalciferol (vitamin D3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome. Life Sci. 2014; 103: 68-72.

Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seely EW, Ganz P, Creager MA. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation 1998; 98: 11158-63.

Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. Mitochondrial dysfunction in autism. JAMA. 2010; 304: 2389-96.

Goh S, Dong Z, Zhang Y, DiMauro S, Peterson BS. Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: Evidence from brain imaging. JAMA Psychiatry. 2014; 71: 665-71.

Haney AF, Weinberg JB. Reduction of the intraperitoneal inflammation associated with endometriosis by treatment with medroxyprogesterone acetate. Am J Obstet Gynecol. 1988; 159: 450-54.

Kern JK, Geier DA, Sykes LK, Geier MR. Relevance of neuro-inflammation and encephalitis in autism. Front Cell Neu-rosci. 2016; 9: 519.

Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, Parmentier M, Detheux M. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003; 278: 25481-89.

MacFabe DF. Short-chain fatty acid fermentation products of the gut microbiome: Implications in autism spectrum disorders. Microb Ecol Heal Dis. 2012.

MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP. Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res. 2007; 176: 149-69.

MacFabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP. Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder. Behav Brain Res. 2011; 217: 47-54.

Mohammadi M, Abdi M, Alidadi M, Mohamed W, Zibara K, Ragerdi I. Medroxyprogesterone acetate attenuates demyelination, modulating microglia activation, in a cuprizone neurotoxic demyelinating mouse model. 2021; 10: 57-68.

Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, Altaye M, Wills-Karp M. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006; 172: 198-205.

Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR, Piven J, Crawley JN. Sociability and preference for social novelty in five inbred strains: An approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004; 3: 287-302.

Narita M, Oyabu A, Imura Y, Kamada N, Yokoyama T, Tano K, Uchida A, Narita N. Nonexploratory movement and behavioral alterations in a thalidomide or valproic acid-induced autism model rat. Neurosci Res. 2010; 66: 2-6.

Oliveira G, Diogo L, Grazina M, Garcia P, Ataíde A, Marques C, Miguel T, Borges L, Vicente A.M, Oliveira CR. Mitochondrial dysfunction in autism spectrum disorders: A population-based study. Dev Med Child Neurol. 2005; 47:185-89.

Oswald DP, Sonenklar NA. Medication use among children with autism spectrum disorders. J Child Adolesc Psychopharmacol. 2007; 17: 348-55.

Pazol K, Wilson ME, Wallen K. Medroxyprogesterone acetate antagonizes the effects of estrogen treatment on social and sexual behavior in female macaques. J Clin Endocrinol Metab. 2004; 89: 2998-06.

Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Maggi E, Barkley MS. Medroxyprogesterone acetate decreases Th1, Th17, and increases Th22 responses via AhR signaling which could affect susceptibility to infections and inflammatory disease. Front Immunol. 2019; 10: 1-15.

Ross HE, Guo Y, Coleman K, Ousley O, Miller AH. Association of IL-12p70 and IL-6: IL-10 ratio with autism-related behaviors in 22q11.2 deletion syndrome: A preliminary report. Brain Behav Immun. 2013; 31, 76-81.

Schneider T, Przewłocki R. Behavioral alterations in rats prenatally to valproic acid: Animal model of autism. Neuropsychopharmacology. 2005; 30, 944-57.

Sharma R, Rahi S, Mehan S. Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: Insights from behavioral and biochemical evidence. Toxicol Reports. 2019; 6: 164-75.

Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, Cain DP. Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: Implications for an animal model of autism. Neuropharmacology. 2008; 54: 901-11.

Silverman JL, Yang M, Lord C, Crawley JN. Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010; 11: 490-502.

Tang G, Gutierrez Rios P, Kuo SH, Akman HO, Rosoklija G, Tanji K, Dwork A, Schon EA, DiMauro S, Goldman J, Sulzer D. Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis. 2013; 54: 349-61.

Tiwari A, Khera R, Rahi S, Mehan S, Makeen HA, Khormi YH, Rehman MU, Khan A. Neuroprotective effect of α‐mangostin in the ameliorating propionic acid‐induced experimental model of autism in wistar rats. Brain Sci. 2021; 11: 1-23.

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005; 57: 304.

Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T. Effect of medroxyprogesterone acetate on vascular inflammatory markers in postmenopausal women receiving estrogen. Circulation 2002; 105: 1436-39.

Whitton PS. Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol. 2007; 150: 963-76.

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Published

2022-06-16

How to Cite

Bozkurt, M. F., M. N. Bhaya, İbrahim H. . Sever, B. . Özkul, and O. Erbaş. “Medroxyprogesterone Acetate Improves Propionic Acid-Induced Autism Rat Model and Magnetic Resonance Spectroscopic Correlation”. Bangladesh Journal of Pharmacology, vol. 17, no. 2, June 2022, pp. 56-65, doi:10.3329/bjp.v17i2.59412.

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Research Articles