Effects of GABA Supplementation on Grooming Behavior and Social Interaction in a Propionic Acid-Induced Rat Model of Autism
DOI:
https://doi.org/10.54878/sgp7fp60Keywords:
Autism Spectrum Disorder (ASD), Propionic acid (PPA), Gamma-aminobutyric acid (GABA), Social interaction, Grooming, Repetitive behaviorAbstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors. Propionic acid (PPA)-induced rodent models are commonly used to study ASD-like behaviors and evaluate potential therapies. This study investigated the therapeutic potential of gamma-aminobutyric acid (GABA) supplementation in mitigating PPA-induced behavioral deficits. Methods: Forty male Western Albino rats were divided into four groups: control, PPA-treated, GABA-treated, and PPA-GABA-treated. Behavioral assessments were conducted using the three-chamber social test to evaluate social interaction and repetitive behaviors. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post-hoc test. Results: PPA administration significantly impaired social interaction without causing significant changes in repetitive grooming behaviors compared to the control group, as evidenced by reduced time spent in the social chamber and increased time in the object chamber. GABA supplementation significantly improved social interaction, while causing a slight but non-significant increase in repetitive grooming behaviors. Conclusion: GABA supplementation demonstrated partial therapeutic effects in mitigating the social deficits induced by PPA administration in a rodent model of ASD. However, the observed increase in grooming behavior highlights the complex role of GABA in modulating ASD-like symptoms, suggesting the need for further investigation into its dual behavioral effects.
References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
Emberti Gialloreti, L., Mazzone, L., Benvenuto, A., Fasano, A., Alcon, A. G., Kraneveld, A., Moavero, R., Raz, R., Riccio, M. P., Siracusano, M., Zachor, D. A., Marini, M., & Curatolo, P. (2019). Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations. Journal of clinical medicine, 8(2), 217. https://doi.org/10.3390/jcm8020217
World Health Organization. (2021). Autism spectrum disorders. Retrieved September 21, 2024, from https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders
Sauer, A. K., Stanton, J. E., Hans, S., & Grabrucker, A. M. (2021). Autism Spectrum Disorders: Etiology and Pathology. In A. M. Grabrucker (Ed.), Autism Spectrum Disorders. Exon Publications.
Meeking, M. M., MacFabe, D. F., Mepham, J. R., Foley, K. A., Tichenoff, L. J., Boon, F. H., Kavaliers, M., & Ossenkopp, K. P. (2020). Propionic acid induced behavioural effects of relevance to autism spectrum disorder evaluated in the hole board test with rats. Progress in neuro-psychopharmacology & biological psychiatry, 97, 109794. https://doi.org/10.1016/j.pnpbp.2019.109794
Bonnet, U., Bingmann, D., & Wiemann, M. (2000). Intracellular pH modulates spontaneous and epileptiform bioelectric activity of hippocampal CA3-neurones. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 10(2), 97–103. https://doi.org/10.1016/s0924-977x(99)00063-2
El-Ansary, A. K., Ben Bacha, A., & Kotb, M. (2012). Etiology of autistic features: the persisting neurotoxic effects of propionic acid. Journal of neuroinflammation, 9, 74. https://doi.org/10.1186/1742-2094-9-74
Sever, I. H., Ozkul, B., Bozkurt, M. F., & Erbas, O. (2022). Therapeutic effect of finasteride through its antiandrogenic and antioxidant role in a propionic acid-induced autism model: Demonstrated by behavioral tests, histological findings and MR spectroscopy. Neuroscience letters, 779, 136622. https://doi.org/10.1016/j.neulet.2022.136622
Sahin, K., Orhan, C., Karatoprak, S., Tuzcu, M., Deeh, P. B. D., Ozercan, I. H., Sahin, N., Bozoglan, M. Y., Sylla, S., Ojalvo, S. P., & Komorowski, J. R. (2022). Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats. Nutrients, 14(6), 1280. https://doi.org/10.3390/nu14061280
Abujamel, T. S., Al-Otaibi, N. M., Abuaish, S., AlHarbi, R. H., Assas, M. B., Alzahrani, S. A., Alotaibi, S. M., El-Ansary, A., & Aabed, K. (2022). Different Alterations in Gut Microbiota between Bifidobacterium longumand Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism. Nutrients, 14(3), 608. https://doi.org/10.3390/nu14030608
Khera, R., Mehan, S., Bhalla, S., Kumar, S., Alshammari, A., Alharbi, M., & Sadhu, S. S. (2022). Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism. Molecules (Basel, Switzerland), 27(3), 889. https://doi.org/10.3390/molecules27030889
Abuaish, S., Al-Otaibi, N. M., Aabed, K., Abujamel, T. S., Alzahrani, S. A., Alotaibi, S. M., Bhat, R. S., Arzoo, S., Algahtani, N., Moubayed, N. M., & El-Ansary, A. (2022). The Efficacy of Fecal Transplantation and Bifidobacterium Supplementation in Ameliorating Propionic Acid-Induced Behavioral and Biochemical Autistic Features in Juvenile Male Rats. Journal of molecular neuroscience : MN, 72(2), 372–381. https://doi.org/10.1007/s12031-021-01959-8
Sharma, A. R., Batra, G., Saini, L., Sharma, S., Mishra, A., Singla, R., Singh, A., Singh, R. S., Jain, A., Bansal, S., Modi, M., & Medhi, B. (2022). Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure. CNS & neurological disorders drug targets, 21(5), 399–408. https://doi.org/10.2174/1871527320666210806165430
Silverman, J. L., Yang, M., Lord, C., & Crawley, J. N. (2010). Behavioural phenotyping assays for mouse models of autism. Nature reviews. Neuroscience, 11(7), 490–502. https://doi.org/10.1038/nrn2851
Lobzhanidze, G., Lordkipanidze, T., Zhvania, M., Japaridze, N., MacFabe, D. F., Pochkidze, N., Gasimov, E., & Rzaev, F. (2019). Effect of propionic acid on the morphology of the amygdala in adolescent male rats and their behavior. Micron (Oxford, England : 1993), 125, 102732. https://doi.org/10.1016/j.micron.2019.102732
Cohen-Mansfield, J., & Jensen, B. (2007). Dressing and grooming: preferences of community-dwelling older adults. Journal of gerontological nursing, 33(2), 31–39. https://doi.org/10.3928/00989134-20070201-07
Prokop, P., Fančovičová, J., & Fedor, P. (2014). Parasites enhance self-grooming behaviour and information retention in humans. Behavioural processes, 107, 42–46. https://doi.org/10.1016/j.beproc.2014.07.017
Liu, H., Huang, X., Xu, J., Mao, H., Li, Y., Ren, K., Ma, G., Xue, Q., Tao, H., Wu, S., & Wang, W. (2021). Dissection of the relationship between anxiety and stereotyped self-grooming using the Shank3Bmutant autistic model, acute stress model and chronic pain model. Neurobiology of stress, 15, 100417. https://doi.org/10.1016/j.ynstr.2021.100417
Gillott, A., & Standen, P. J. (2007). Levels of anxiety and sources of stress in adults with autism. Journal of intellectual disabilities : JOID, 11(4), 359–370. https://doi.org/10.1177/1744629507083585
Dey, R., & Chattarji, S. (2022). The same stress elicits different effects on anxiety-like behavior in rat models of Fmr1-/y and Pten+/. Behavioural brain research, 428, 113892. https://doi.org/10.1016/j.bbr.2022.113892
Mu, M. D., Geng, H. Y., Rong, K. L., Peng, R. C., Wang, S. T., Geng, L. T., Qian, Z. M., Yung, W. H., & Ke, Y. (2020). A limbic circuitry involved in emotional stress-induced grooming. Nature communications, 11(1), 2261. https://doi.org/10.1038/s41467-020-16203-x
Parrella, N. F., Hill, A. T., Dipnall, L. M., Loke, Y. J., Enticott, P. G., & Ford, T. C. (2024). Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review. Journal of psychiatric research, 169, 113–125. https://doi.org/10.1016/j.jpsychires.2023.11.014
Abd El-Hady, A. M., Gewefel, H. S., Badawi, M. A., & El-Morsy, E. M. (2017). Gamma-aminobutyric acid ameliorates gamma rays-induced oxidative stress in the small intestine of rats. Journal of Basic and Applied Zoology, 78(2), Article 2. https://doi.org/10.1186/s41936-017-0005-3
Schwartzer, J. J., Careaga, M., Onore, C. E., Rushakoff, J. A., Berman, R. F., & Ashwood, P. (2013). Maternal immune activation and strain specific interactions in the development of autism-like behaviors in mice. Translational psychiatry, 3(3), e240. https://doi.org/10.1038/tp.2013.16
Lo, S. C., Scearce-Levie, K., & Sheng, M. (2016). Characterization of social behaviors in caspase-3 deficient mice. Scientific reports, 6, 18335. https://doi.org/10.1038/srep18335
Friard, O., & Gamba, M. (2016). BORIS: A free, versatile open-source event-logging software for video/audio coding and live observations. Methods in Ecology and Evolution, 7(11), 1325–1330. https://doi.org/10.1111/2041-210X.12584
Choi, J., Lee, S., Won, J., Jin, Y., Hong, Y., Hur, T. Y., Kim, J. H., Lee, S. R., & Hong, Y. (2018). Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model. PloS one, 13(2), e0192925. https://doi.org/10.1371/journal.pone.0192925
Zhang, Y., Peng, L., & Song, W. (2020). Mitochondria hyperactivity contributes to social behavioral impairments. Signal transduction and targeted therapy, 5(1), 126. https://doi.org/10.1038/s41392-020-00239-y
Lee, H., Kim, H., Chang, Y. B., Han, K., Choi, H.-S., Han, S. H., & Suh, H. J. (2024). Lactobacillus brevis M2-Fermented Whey Protein Hydrolysate Increases Slow-Wave Sleep via GABAA Receptors in Rodent Models. Foods, 13(13), 2049. https://doi.org/10.3390/foods13132049
Cellot, G., & Cherubini, E. (2014). GABAergic signaling as therapeutic target for autism spectrum disorders. Frontiers in pediatrics, 2, 70. https://doi.org/10.3389/fped.2014.00070
Han, S., Tai, C., Westenbroek, R. E., Yu, F. H., Cheah, C. S., Potter, G. B., Rubenstein, J. L., Scheuer, T., de la Iglesia, H. O., & Catterall, W. A. (2012). Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission. Nature, 489(7416), 385–390. https://doi.org/10.1038/nature11356
Han, S., Tai, C., Jones, C. J., Scheuer, T., & Catterall, W. A. (2014). Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism. Neuron, 81(6), 1282–1289. https://doi.org/10.1016/j.neuron.2014.01.016
Gandal, M. J., Sisti, J., Klook, K., Ortinski, P. I., Leitman, V., Liang, Y., Thieu, T., Anderson, R., Pierce, R. C., Jonak, G., Gur, R. E., Carlson, G., & Siegel, S. J. (2012). GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Translational psychiatry, 2(7), e142. https://doi.org/10.1038/tp.2012.69
Barros, H. M., Tannhauser, S. L., Tannhauser, M. A., & Tannhauser, M. (1994). The effects of GABAergic drugs on grooming behaviour in the open field. Pharmacology & toxicology, 74(6), 339–344. https://doi.org/10.1111/j.1600-0773.1994.tb01370.x
Petroff, O. A., Hyder, F., Mattson, R. H., & Rothman, D. L. (1999). Topiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy. Neurology, 52(3), 473–478. https://doi.org/10.1212/wnl.52.3.473
Walker, M. C., & Sander, J. W. (1996). Topiramate: a new antiepileptic drug for refractory epilepsy. Seizure, 5(3), 199–203. https://doi.org/10.1016/s1059-1311(96)80036-7
Allen, M. J., Sabir, S., & Sharma, S. (2023). GABA Receptor. In StatPearls. StatPearls Publishing.
Besag F. M. (2001). Behavioural effects of the new anticonvulsants. Drug safety, 24(7), 513–536. https://doi.org/10.2165/00002018-200124070-00004
