EMIRATES SCHOLAR DIRECTORY | Publisher Website

Articles

Vol. 3 No. 1 (2026): International Journal for Autism Challenges & Solution

Gender-Related Disparities in induced biochemical autistic features using propionic acid rat model

  • Hadeer El-Salamony,  
  • Farouk Aly Hanan,  
  • Naima Mohamed,  
  • Wagdy Khalil,  
Submitted
May 5, 2026
Published
2026-06-09

Abstract

The dramatical increase in autism spectrum disorder (ASD) prevalence as a neurodevelopmental disorder highlighted the urgent need for early detection and intervention as its symptoms vary across individuals. The question of whether females and males show ASD differently is still up for debate. Research examining the relationship between sex and symptoms of autism and other psychiatric issues typically lacks a general population comparison group, making it difficult to determine whether observed differences are unique to autism or reflect general development patterns. Methods: The present study aimed to understanding sex-related differences in vulnerability to develop autistic features in propionic acid (PPA) induced autism in the rodent model. Thirty-two Wistar albino juvenile male and female rats were divided equally into four groups. Group 1 received saline and served as a control. Group 2 received buffered PPA at 250 mg/kg b.w/day for three consecutive days. While sixteen female Wistar albino juvenile rats were divided into two groups (8 rats/group) as follows: Group 3 received saline and served as a control. While, Group 4 received buffered PPA at 250 mg/kg b.w/day for three consecutive days. Serotonin, dopamine (DA), gamma-aminobutyric acid (GABA) and glutamate were measured. Brain-derived neurotrophic factor (BDNF), caspase 9 and NF-κB were evaluated in all groups. Moreover, Expression Analysis of neurodevelopmental regulator genes (FMR1 and FOXP1) and inflammatory gene (COX-1) was detected. Results: PPA administration significantly reduced dopamine, GABA, and FMR1 gene with significant elevation in serotonin, glutamate, BDNF, caspase 9, NF-κB and Expression of FOXP1 and COX-1 genes. Conclusion: Our research highlighted different biochemical parameters that can be promising biomarkers for ASD. the study also discussed sex differences found in animal models of ASD, to provide a possible explanation of the neurological mechanisms underpinning the different presentation of autistic symptoms in males and females.

References

  1. Jiang, Y., Dang, W., Nie, H., Kong, X., Jiang, Z., & Guo, J. (2023). Omega-3 polyunsaturated fatty acids and/or vitamin D in autism spectrum disorders: a systematic review. Frontiers in Psychiatry, 14, 1238973. https://doi.org/10.3389/fpsyt.2023.1238973
  2. Alnasser, Y. K. A. (2023). Autism Spectrum Disorder: A Comprehensive Review of Literature. Scholars Academic Journal of Biosciences, 11(03), 116–121. https://doi.org/10.36347/sajb.2023.v11i03.007
  3. Mandalà, G., Mandalà, S., & Capuana, L. (2025). Autism Spectrum Disorders: A Literature review of Traditional therapies and Emerging Treatment frontiers. American Journal of Medical and Clinical Research & Reviews, 04(06), 01–14. https://doi.org/10.58372/2835-6276.1307
  4. Turpin, V., Schaffhauser, M., Thabault, M., Aubert, A., Joffre, C., Balado, E., Longueville, J., Francheteau, M., Burucoa, C., Pichon, M., Layé, S., & Jaber, M. (2023). Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets. Scientific Reports, 13(1), 11235. https://doi.org/10.1038/s41598-023-38423-z
  5. Shaw, K. A., Williams, S., Patrick, M. E., Valencia-Prado, M., Durkin, M. S., Howerton, E. M., Ladd-Acosta, C. M., Pas, E. T., Bakian, A. V., Bartholomew, P., Nieves-Muñoz, N., Sidwell, K., Alford, A., Bilder, D. A., DiRienzo, M., Fitzgerald, R. T., Furnier, S. M., Hudson, A. E., Pokoski, O. M., . . . Maenner, M. J. (2025). Prevalence and early identification of autism spectrum disorder among children aged 4 and 8 years — Autism and Developmental Disabilities Monitoring Network, 16 sites, United States, 2022. MMWR Surveillance Summaries, 74(2), 1–22. https://doi.org/10.15585/mmwr.ss7402a1
  6. Stroth, S., Tauscher, J., Wolff, N., Küpper, C., Poustka, L., Roepke, S., Roessner, V., Heider, D., & Kamp-Becker, I. (2022). Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder. Molecular Autism, 13(1), 11. https://doi.org/10.1186/s13229-022-00491-9
  7. Salari, N., Rasoulpoor, S., Rasoulpoor, S., Shohaimi, S., Jafarpour, S., Abdoli, N., Khaledi-Paveh, B., & Mohammadi, M. (2022). The global prevalence of autism spectrum disorder: a comprehensive systematic review and meta-analysis.Italian Journal of Pediatrics, 48(1), 112. https://doi.org/10.1186/s13052-022-01310-w
  8. Halladay, A. K., Bishop, S., Constantino, J. N., Daniels, A. M., Koenig, K., Palmer, K., Messinger, D., Pelphrey, K., Sanders, S. J., Singer, A. T., Taylor, J. L., & Szatmari, P. (2015). Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Molecular Autism, 6(1), 36. https://doi.org/10.1186/s13229-015-0019-y
  9. Hull, L., Petrides, K. V., & Mandy, W. (2020). The Female Autism Phenotype and Camouflaging: a Narrative Review. Review Journal of Autism and Developmental Disorders, 7(4), 306–317. https://doi.org/10.1007/s40489-020-00197-9
  10. Lai, M., Hull, L., Mandy, W., Chakrabarti, B., Nordahl, C. W., Lombardo, M. V., Ameis, S. H., Szatmari, P., Baron‐Cohen, S., Happé, F., & Livingston, L. A. (2020). Commentary: ‘Camouflaging’ in autistic people – reflection on Fombonne (2020). Journal of Child Psychology and Psychiatry, 62(8). https://doi.org/10.1111/jcpp.13344
  11. Lai, M., Lombardo, M. V., Ruigrok, A. N., Chakrabarti, B., Auyeung, B., Szatmari, P., Happé, F., & Baron-Cohen, S. (2016). Quantifying and exploring camouflaging in men and women with autism. Autism, 21(6), 690–702. https://doi.org/10.1177/1362361316671012
  12. Fombonne, E. (2020). Camouflage and autism. Journal of Child Psychology and Psychiatry, 61(7), 735–738. https://doi.org/10.1111/jcpp.13296
  13. Robinson, E. B., Lichtenstein, P., Anckarsäter, H., Happé, F., & Ronald, A. (2013). Examining and interpreting the female protective effect against autistic behavior. Proceedings of the National Academy of Sciences, 110(13), 5258–5262. https://doi.org/10.1073/pnas.1211070110
  14. Li, K., Zhang, Q., Niu, D., & Xing, H. (2020). Mining mIRNAs’ expressions in glioma based on GEO database and their effects on biological functions. BioMed Research International, 2020(1), 5637864. https://doi.org/10.1155/2020/5637864
  15. Aly, H. F., Salamony, H. E. E., Ali, E., Mohamed, M., Elbaset, M., & Mohamed, N. (2025). Exploring the therapeutic efficiency of the synergetic role of omega-3 and vitamin E in propionic Acid-Induced autistic features in juvenile rat model. International Journal of Theoretical and Applied Research, 4(1), 668–681. https://doi.org/10.21608/ijtar.2025.380082.1122
  16. Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2024). An update on Psychopharmacological treatment of autism spectrum disorder. FOCUS the Journal of Lifelong Learning in Psychiatry, 22(2), 198–211. https://doi.org/10.1176/appi.focus.24022006
  17. Barbosa, A. G., Pratesi, R., Paz, G. S. C., Santos, M. a. a. L. D., Uenishi, R. H., Nakano, E. Y., Gandolfi, L., & Pratesi, C. B. (2020). Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder. Scientific Reports, 10(1), 17348. https://doi.org/10.1038/s41598-020-74239-x
  18. El-Ansary, A., Zayed, N., Al-Ayadhi, L., Qasem, H., Anwar, M., Meguid, N. A., Bhat, R. S., Doşa, M. D., Chirumbolo, S., & Bjørklund, G. (2019). GABA synaptopathy promotes the elevation of caspases 3 and 9 as pro-apoptotic markers in Egyptian patients with autism spectrum disorder. Acta Neurologica Belgica, 121(2), 489–501. https://doi.org/10.1007/s13760-019-01226-z
  19. Tamizkar, K. H., Badrlou, E., Aslani, T., Brand, S., Arsang-Jang, S., Ghafouri-Fard, S., & Taheri, M. (2021). Dysregulation of NF-ΚB-Associated LNCRNAs in autism spectrum disorder. Frontiers in Molecular Neuroscience, 14, 747785. https://doi.org/10.3389/fnmol.2021.747785
  20. Young, A. M. H., Campbell, E., Lynch, S., Suckling, J., & Powis, S. J. (2011). Aberrant NF-KaPPAB expression in autism spectrum condition: a mechanism for neuroinflammation. Frontiers in Psychiatry, 2, 27. https://doi.org/10.3389/fpsyt.2011.00027
  21. Fyke, W., & Velinov, M. (2021). FMR1 and autism, an intriguing connection revisited. Genes, 12(8), 1218. https://doi.org/10.3390/genes12081218
  22. Al-Ali ZA, Al-Mousawi MR, Al-Karaqully AJ, Alattabi AS, Ali MS, Mahdi LH, et al (2024) Role of FOXP1 (SNPS) Gene in Autism Spectrum Disorder Pathogenesis. Autism-Open Access. 14:397
  23. Kamal, D. a. M., Abidin, S. Z., Saudi, W. S. W., Kumar, J., & Bellato, A. (2025). Roles of prostaglandins and cyclooxygenases in autism Spectrum Disorder: A Comprehensive review. Current Behavioral Neuroscience Reports, 12(1). https://doi.org/10.1007/s40473-024-00294-7
  24. Bukhari, S. I., Alfawaz, H., Al-Dbass, A., Bhat, R. S., Moubayed, N. M., Bukhari, W., Hassan, S. A., Merghani, N., Elsamaligy, S., & El-Ansary, A. (2020). Efficacy of Novavit in ameliorating the neurotoxicity of propionic acid. Translational Neuroscience, 11(1), 134–146. https://doi.org/10.1515/tnsci-2020-0103
  25. Nijjar, S., Maddison, D., Meigh, L., De Wolf, E., Rodgers, T., Cann, M. J., & Dale, N. (2020). Opposing modulation of Cx26 gap junctions and hemichannels by CO 2. The Journal of Physiology, 599(1), 103–118. https://doi.org/10.1113/jp280747
  26. Cotrina, M. L., Ferreiras, S., & Schneider, P. (2019). High prevalence of self‐reported autism spectrum disorder in the Propionic Acidemia Registry. JIMD Reports, 51(1), 70–75. https://doi.org/10.1002/jmd2.12083
  27. Alfawaz, H., Al-Onazi, M., Bukhari, S. I., Binobead, M., Othman, N., Algahtani, N., Bhat, R. S., Moubayed, N. M. S., Alzeer, H. S., & El-Ansary, A. (2018). The independent and combined effects of omega-3 and vitamin B12 in ameliorating propionic acid induced biochemical features in juvenile rats as rodent model of autism. Journal of Molecular Neuroscience, 66(3), 403–413. https://doi.org/10.1007/s12031-018-1186-z
  28. Hamed, M. A., Naser, A. F. A., Aboutabl, M. E., Osman, A. F., Hassan, E. E. S., Aziz, W. M., Khalil, W. K. B., Farghaly, A. A., & El-Hagrassi, A. M. (2021). Bioactive compounds and therapeutic role ofBrassica oleraceaL. seeds in rheumatoid arthritis ratsviaregulating inflammatory signalling pathways and antagonizing interleukin-1 receptor action. Biomarkers, 26(8), 788–807. https://doi.org/10.1080/1354750x.2021.1999504
  29. Elateek, S. Y., Salem, L. M., Ahmed, E. S., & Khalil, W. K. (2021). Staphylococcus aureus isolates from hospital clinics induce ROS-mediated DNA damage, apoptosis and gene expression alterations in male mice. Gene Reports, 23, 101028. https://doi.org/10.1016/j.genrep.2021.101028
  30. Sayed, A. A., Abdullah, M. S., WalyEldeen, A. A., Sayed, R. M. S., Gabre, R. M., Ibrahim, S. A., & Hassan, H. (2025). Cicer arietinum extract as antitumor and protective agent against Ehrlich Solid Carcinoma-bearing mice. BMC Complementary Medicine and Therapies, 25(1), 325. https://doi.org/10.1186/s12906-025-05061-z
  31. Elhinnawi, M. A., Mohareb, R. M., Rady, H. M., Khalil, W. K., Elhalim, M. M. A., & Elmegeed, G. A. (2018). Novel pregnenolone derivatives modulate apoptosis via Bcl-2 family genes in hepatocellular carcinoma in vitro. The Journal of Steroid Biochemistry and Molecular Biology, 183, 125–136. https://doi.org/10.1016/j.jsbmb.2018.06.006
  32. Refaie, A. A., Ramadan, A., Sabry, N. M., Khalil, W. K. B., & Mossa, A. H. (2020). Over-gene expression in the apoptotic, oxidative damage and liver injure in female rats exposed to butralin. Environmental Science and Pollution Research, 27(25), 31383–31393. https://doi.org/10.1007/s11356-020-09416-6
  33. Akbulut, M. C., Altuntas, İ., Tomruk, C., Uyanıkgil, Y., & Erbas, O. (2024b). Fenofibrate improves the propionic Acid-Induced autism model in rats via decrease brain galectin-3 level. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.4688406
  34. Durankuş, F., Budak, K., Albayrak, Y., Sever, İ. H., Özkul, B., Uyanıkgil, Y., Albayrak, N., & Erbas, O. (2023). Atorvastatin improves the propionic Acid-Induced autism in rats: the roles of Sphingosine-1-Phosphate and anti-inflammatory action. Cureus, 15(3), e36870. https://doi.org/10.7759/cureus.36870
  35. Hwang, Y. K., & Oh, J. S. (2025). Interaction of the vagus nerve and serotonin in the Gut–Brain axis. International Journal of Molecular Sciences, 26(3), 1160. https://doi.org/10.3390/ijms26031160
  36. Ali, E., Hassan, M., Abbas, O., EElmalahy, H., & Almaaty, A. A. (2020). Uritica dioica improves brain dysfunctions in propionic acid autistic like rat model through brain monoamines and mitochondrial energy. African Journal of Biological Sciences, 16(1), 207–231. https://doi.org/10.21608/ajbs.2020.133010
  37. Ali, E., Hassan, M., Abbas, O., EElmalahy, H., & Almaaty, A. A. (2020). Uritica dioica improves brain dysfunctions in propionic acid autistic like rat model through brain monoamines and mitochondrial energy. African Journal of Biological Sciences, 16(1), 207–231. https://doi.org/10.21608/ajbs.2020.133010
  38. Bhat, R. S., Alonazi, M., Al-Daihan, S., & El-Ansary, A. (2023). Prenatal SSRI exposure increases the risk of autism in rodents via aggravated oxidative stress and neurochemical changes in the brain. Metabolites, 13(2), 310. https://doi.org/10.3390/metabo13020310
  39. Munro, C. A., McCaul, M. E., Wong, D. F., Oswald, L. M., Zhou, Y., Brasic, J., Kuwabara, H., Kumar, A., Alexander, M., Ye, W., & Wand, G. S. (2006). Sex differences in striatal dopamine release in healthy adults. Biological Psychiatry, 59(10), 966–974. https://doi.org/10.1016/j.biopsych.2006.01.008
  40. Andersen, S., & Teicher, M. (2000). Sex differences in dopamine receptors and their relevance to ADHD. Neuroscience & Biobehavioral Reviews, 24(1), 137–141. https://doi.org/10.1016/s0149-7634(99)00044-5
  41. Weiss, L. A., Abney, M., Cook, E. H., & Ober, C. (2004). Sex-Specific genetic architecture of whole blood serotonin

Downloads

Download data is not yet available.

Similar Articles

1-10 of 16

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

<< < 1 2 
Empowering Knowledge · Advancing Communities

Founded in 2019, Emirates Scholar Center for Research & Studies is the UAE's first specialized entity dedicated to scientific indexing, publishing, and promoting research across diverse fields — contributing to UAE Vision 2071 and a knowledge-based economy.

15+ Peer-Reviewed Journals
9+ Index Databases
2019 Est. Abu Dhabi, UAE
📚
Browse All Journals
Explore 15+ peer-reviewed open-access journals across business, health, education, technology, and social sciences.
View Journals →
🎓
Training Academy
Build your research and publishing skills with our academic training programs, workshops, and capacity-building courses.
Explore Training →
✍️
News & Articles
Explore our ongoing initiatives and milestones, and remain informed about our continuous achievements.
Latest News →
📍 Level 36, Etihad Towers – T3, Abu Dhabi, UAE 📧 info@emiratesscholar.com 📞 +971 2 409 3159
Empowering knowledge · Advancing community
Emirates Scholar Center for Research & Studies
Level 36, Etihad Towers – T3, Abu Dhabi, UAE · P.O. Box 28686
Emirates Scholar
  • Submit Manuscript