نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی کارشناسی ارشد فیزیولوژی پزشکی، گروه فیزیولوژی و فارماکولوژی ، دانشکده پزشکی، دانشگاه علوم پزشکی سبزوار، ایران

2 دانشیار گروه فیزیولوژی و فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی سبزوار، ایران

3 استاد گروه فیزیولوژی و فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی سبزوار، ایران

4 استادیار گروه طب سنتی، دانشکده پزشکی، دانشگاه علوم پزشکی سبزوار، سبزوار، ایران

5 استاد مرکز تحقیقات روانپزشکی و علوم رفتاری، دانشگاه علوم پزشکی مشهد، مشهد، ایران

چکیده

زمینه: اختلال طیف اوتیسم (ASD) نوعی اختلال عصبی است که رفتار تکراری و اختلال ارتباط اجتماعی دو علائم اصلی آن است. شیر شتر به دلیل داشتن خواص آنتی‌اکسیدانی، تعدیل‌کننده سیستم ایمنی و ضدالتهاب ممکن است بتواند در درمان اوتیسم مؤثر واقع شود.

مواد و روش‌ها: موش‌های باردار به‌طور تصادفی به‌صورت داخل صفاقی 500 میلی‌گرم در کیلوگرم والپروئیک اسید (VPA) در روز5 /12 حاملگی تزریق شد. سپس نوزادهای نر به پنج گروه کنترل، گروه VPA، گروه شیر خام شتر + ریسپریدون و گروه شیر شتر پاستوریزه + ریسپریدون، و ریسپریدون تقسیم شدند. برای دوره درمان ریسپریدون (mg/kg 2/0) تزریق شد و شیر خام و پاستوریزه شده شتر روزانه (ml/kg 10) به مدت 42 روز به موش‌ها داده شد. آزمایش‌های تداخل رفتاری-اجتماعی و تکراری در ابتدا و انتهای دوره درمان سنجیده شد.

نتایج: شاخص‌های جامعه‌پذیری و ترجیح اجتماعی زاده‌های مادرانی که VPA دریافت کردند کاهش معناداری داشت. همچنین رفتارهای تکراری خود آراستگی در این حیوانات افزایش یافت. گروه‌های درمانی پس از دریافت رژیم شیر شتر و داروی ریسپریدون رفتارهای اجتماعی و تکراری در آن‌ها بهبود یافت و نسبت به گروه‌های VPA و نیز قبل از درمان اختلاف معناداری داشتند؛ و شاخص‌های اجتماعی افزایش نشان داد. شاخص جامعه‌پذیری، ترجیح اجتماعی، شاخص ترجیح اجتماعی و نیز رفتارهای تکراری در قبل و نیز در بعد درمان بین گروه‌ها به‌طور معنی‌داری (p <0.001) بعد از درمان بهبود یافت.

نتیجه‌گیری: درمان با رژیم شیر شتر رفتارهای اصلی علائم اوتیسم مانند تعاملات اجتماعی و حرکات تکراری را بهبود بخشید.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The effect of camel milk on autism-like behaviors in laboratory mice

نویسندگان [English]

  • Sahar Heydari 1
  • Bahareh Amin 2
  • Akbar Pejhan 3
  • Seyed Jamal Mirmoosavi 4
  • Mohammad Mohammadzadeh 5

1 Master student of Medical Physiology, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Iran

2 Associate Professor, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Iran

3 Professor of Physiology, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Iran

4 Assistant Professor, Department of Traditional Medicine, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

5 Professor of Physiology, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran

چکیده [English]

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental syndrome with two main symptoms: repetitive behavior and social interaction disorder. Camel milk, due to its antioxidant, immune-modulating, anti-inflammatory, and anti-apoptotic properties maybe have beneficial effects on ASD.

Materials and Methods: Pregnant rats were injected intraperitoneally on day 12.5 of gestation with 500 mg/kg valproic acid. Then male neonatal rats were divided into five groups: Control group, valproic acid group, camel raw milk group + risperidone, and boiled camel milk group + risperidone. For the treatment period, rats have injected with risperidone (0.2 mg/kg) three times a week, and raw and boiled camel milk was given daily (10 ml/kg) for 42 days. Experiments of social interaction and repetitive behavior were measured at the beginning and end of the treatment period.

Results: The offspring of mothers who received valproic acid had problems in social interactions, and sociability and social preference indexes were significantly reduced. Repetitive self-glooming behaviors also increased in VPA-rats. The treatment groups improved their social and repetitive behaviors after receiving camel milk and risperidone and were significantly different from the valproic acid and pre-treatment groups. Moreover, sociability and social preference indexes showed an increase after treatment with camel milk. Sociability index, social preference, social preference index, and repetitive behaviors before and after treatment between groups improved significantly (p <0.001) after treatment.

Conclusion: Treatment with a camel milk diet improved the main behaviors of autism symptoms, such as social interactions and repetitive movements

کلیدواژه‌ها [English]

  • Autism
  • Behavior test
  • Camel milk
  • Valproic acid
  1. Vieta E. DSM-5.1. Acta Psychiatr Scand. 2016 Sep;134(3):187-8. PubMed PMID: 27500779. Epub 2016/08/09.
  2. Rosenhan D. Seligman. ME (1995). Abnormal psychology. New York: Academic Press.
  3. Jin Y, Wee CY, Shi F, Thung KH, Yap PT, Shen D. Identification of Infants at Risk for Autism Using Multi-parameter Hierarchical White Matter Connectomes. Mach Learn Med Imaging. 2015;9352:170-7. PubMed PMID: 26900607. Pubmed Central PMCID: Pmc4758369. Epub 2016/02/24.
  4. Yenkoyan K, Grigoryan A, Fereshetyan K, Yepremyan D. Advances in understanding the pathophysiology of autism spectrum disorders. Behav Brain Res. 2017 Jul 28;331:92-101. PubMed PMID: 28499914. Epub 2017/05/14.
  5. Kellogg M, Meador KJ. Neurodevelopmental Effects of Antiepileptic Drugs. Neurochemical research. 2017 Jul;42(7):2065-70. PubMed PMID: 28424947. Pubmed Central PMCID: Pmc6390972. Epub 2017/04/21.
  6. Ornoy A. Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Reproductive toxicology (Elmsford, NY). 2009 Jul;28(1):1-10. PubMed PMID: 19490988. Epub 2009/06/06.
  7. Inui T, Kumagaya S, Myowa-Yamakoshi M. Neurodevelopmental Hypothesis about the Etiology of Autism Spectrum Disorders. Front Hum Neurosci. 2017;11:354. PubMed PMID: 28744208. Pubmed Central PMCID: Pmc5504094. Epub 2017/07/27.
  8. Lamy M, Erickson CA. Pharmacological management of behavioral disturbances in children and adolescents with autism spectrum disorders. Curr Probl Pediatr Adolesc Health Care. 2018 Oct;48(10):250-64. PubMed PMID: 30262163. Epub 2018/09/29.
  9. Yagil R. Camel milk and its unique anti-diarrheal properties. Isr Med Assoc J. 2013 Jan;15(1):35-6. PubMed PMID: 23484237. Epub 2013/03/15.
  10. Singh R, Mal G, Kumar D, Patil NV, Pathak KML. Camel Milk: An Important Natural Adjuvant. Agric Res. 2017;6(4):327-40.
  11. Hammam ARA. Compositional and therapeutic properties of camel milk: A review. Emirates J Food Agric. 2019;31(3):148-52.
  12. Izadi A, Khedmat L, Mojtahedi SY. Nutritional and therapeutic perspectives of camel milk and its protein hydrolysates: A review on versatile biofunctional properties. J Funct Foods. 2019 2019/09/01/;60:103441.
  13. Al-Ayadhi LY, Elamin NE. Camel milk as a potential therapy as an antioxidant in autism spectrum disorder (ASD). Evid Based Complement Alternat Med. 2013;2013.
  14. Adams CM. Patient report: autism spectrum disorder treated with camel milk. Global Advances in Health and Medicine. 2013;2(6):78-80.
  15. Bashir S, Al-Ayadhi LY. Effect of camel milk on thymus and activation-regulated chemokine in autistic children: double-blind study. Pediatr Res. 2014;75(4):559-63.
  16. Mirza R, Sharma B. Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats. Brain Res Bull. 2019;147:36-46.
  17. Hamzawy MA, El-Ghandour YB, Abdel-Aziem SH, Ali ZH. Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism. Int J Immunopathol Pharmacol. 2018;32:2058738418785514.
  18. Hara Y, Takuma K, Takano E, Katashiba K, Taruta A, Higashino K, et al. Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model. Behav Brain Res. 2015;289:39-47.
  19. Hara Y, Ago Y, Taruta A, Hasebe S, Kawase H, Tanabe W, et al. Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice. Psychopharmacology (Berl). 2017;234(21):3217-28.
  20. Ishola IO, Balogun AO, Adeyemi OO. Novel potential of metformin on valproic acid-induced autism spectrum disorder in rats: involvement of antioxidant defence system. Fundam Clin Pharmacol. 2020;34(6):650-61.
  21. Matsuo K, Yabuki Y, Fukunaga K. 5-aminolevulinic acid inhibits oxidative stress and ameliorates autistic-like behaviors in prenatal valproic acid-exposed rats. Neuropharmacology. 2020;168:107975.
  22. Servadio M, Manduca A, Melancia F, Leboffe L, Schiavi S, Campolongo P, et al. Impaired repair of DNA damage is associated with autistic-like traits in rats prenatally exposed to valproic acid. Eur Neuropsychopharmacol. 2018;28(1):85-96.
  23. Hara Y, Ago Y, Higuchi M, Hasebe S, Nakazawa T, Hashimoto H, et al. Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism. Horm Behav. 2017;96:130-6.
  24. Campolongo M, Kazlauskas N, Falasco G, Urrutia L, Salgueiro N, Höcht C, et al. Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment. 2018;9:36.
  25. Melancia F, Schiavi S, Servadio M, Cartocci V, Campolongo P, Palmery M, et al. Sex-specific autistic endophenotypes induced by prenatal exposure to valproic acid involve anandamide signalling. 2018;175(18):3699-712.
  26. Moldrich RX, Leanage G, She D, Dolan-Evans E, Nelson M, Reza N, et al. Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice. Behav Brain Res. 2013;257:253-64.
  27. Fontes-Dutra M, Della-Flora Nunes G, Santos-Terra J, Souza-Nunes W, Bauer-Negrini G, Hirsch MM, et al. Abnormal empathy-like pro-social behaviour in the valproic acid model of autism spectrum disorder. Behav Brain Res. 2019;364:11-8.
  28. 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.
  29. Zibaee S, Hosseini SMA-R, Yousefi M, Taghipour A, Kiani MA, Noras MR. Nutritional and Therapeutic Characteristics of Camel Milk in Children: A Systematic Review. Electron Physician. 2015;7(7):1523-8.
  30. Al-Ayadhi LY, Elamin NE. Camel Milk as a Potential Therapy as an Antioxidant in Autism Spectrum Disorder (ASD). Evidence-based complementary and alternative medicine : eCAM. 2013;2013:602834.