Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

doi:10.3390/ijms20051074

Review

. 2019 Mar 1;20(5):1074.

doi: 10.3390/ijms20051074.

Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

Asher Ornoy¹, Liza Weinstein-Fudim², Zivanit Ergaz^{3

4}

Affiliations

¹ Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. ornoy@cc.huji.ac.il.
² Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. liza.weinstein-f@mail.huji.ac.il.
³ Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. Zivanit@hadassah.org.il.
⁴ Neonatology Department, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel. Zivanit@hadassah.org.il.

PMID: 30832249
PMCID: PMC6429371
DOI: 10.3390/ijms20051074

Review

Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

Asher Ornoy et al. Int J Mol Sci. 2019.

. 2019 Mar 1;20(5):1074.

doi: 10.3390/ijms20051074.

Authors

Asher Ornoy¹, Liza Weinstein-Fudim², Zivanit Ergaz^{3

4}

Affiliations

¹ Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. ornoy@cc.huji.ac.il.
² Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. liza.weinstein-f@mail.huji.ac.il.
³ Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel. Zivanit@hadassah.org.il.
⁴ Neonatology Department, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel. Zivanit@hadassah.org.il.

PMID: 30832249
PMCID: PMC6429371
DOI: 10.3390/ijms20051074

Abstract

Since the first animal model of valproic acid (VPA) induced autistic-like behavior, many genetic and non-genetic experimental animal models for Autism Spectrum Disorder (ASD) have been described. The more common non-genetic animal models induce ASD in rats and mice by infection/inflammation or the prenatal or early postnatal administration of VPA. Through the establishment of these models, attempts have been made to ameliorate or even prevent ASD-like symptoms. Some of the genetic models have been successfully treated by genetic manipulations or the manipulation of neurotransmission. Different antioxidants have been used (i.e., astaxanthin, green tea, piperine) to reduce brain oxidative stress in VPA-induced ASD models. Agents affecting brain neurotransmitters (donepezil, agmatine, agomelatine, memantine, oxytocin) also successfully reduced ASD-like symptoms. However, complete prevention of the development of symptoms was achieved only rarely. In our recent study, we treated mouse offspring exposed on postnatal day four to VPA with S-adenosine methionine (SAM) for three days, and prevented ASD-like behavior, brain oxidative stress, and the changes in gene expression induced by VPA. In this review, we describe, in addition to our data, the existing literature on the prevention/amelioration of ASD-like symptoms. We also discuss the possible mechanisms underlying some of these phenomena. Finally, we describe some of the clinical trials in children with ASD that were carried out as a result of data from animal studies, especially those with polyunsaturated fatty acids (PUFAs).

Keywords: PUFAs; SAM; VPA; amelioration; animal models of ASD; human ASD; oxytocin; prevention; rodents.

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Conflict of interest statement

The authors declare no conflict of interest.

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References

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[1] Baio J., Wiggins L., Christensen D.L., Maenner M.J., Daniels J., Warren Z., Kurzius-Spencer M., Zahorodny W., Robinson Rosenberg C., White T., et al. Prevalence of Autism Spectrum Disorder among Children Aged 8 Years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveill. Summ. 2018;67:1–23. doi: 10.15585/mmwr.ss6706a1. - DOI - PMC - PubMed

[2] Baio J., Wiggins L., Christensen D.L., Maenner M.J., Daniels J., Warren Z., Kurzius-Spencer M., Zahorodny W., Robinson Rosenberg C., White T., et al. Prevalence of Autism Spectrum Disorder among Children Aged 8 Years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveill. Summ. 2018;67:1–23. doi: 10.15585/mmwr.ss6706a1. - DOI - PMC - PubMed

[3] Kogan M.D., Vladutiu C.J., Schieve L.A., Ghandour R.M., Blumberg S.J., Zablotsky B., Perrin J.M., Shattuck P., Kuhlthau K.A., Harwood R.L., et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018;142:e20174161. doi: 10.1542/peds.2017-4161. - DOI - PMC - PubMed

[4] Kogan M.D., Vladutiu C.J., Schieve L.A., Ghandour R.M., Blumberg S.J., Zablotsky B., Perrin J.M., Shattuck P., Kuhlthau K.A., Harwood R.L., et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018;142:e20174161. doi: 10.1542/peds.2017-4161. - DOI - PMC - PubMed

[5] Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association Publishing; Washington, DC, USA: 2013.

[6] Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association Publishing; Washington, DC, USA: 2013.

[7] Ergaz Z., Weinstein-Fudim L., Ornoy A. Genetic and non-genetic animal models for autism spectrum disorders (ASD) Reprod. Toxicol. 2016;64:116–140. doi: 10.1016/j.reprotox.2016.04.024. - DOI - PubMed

[8] Ergaz Z., Weinstein-Fudim L., Ornoy A. Genetic and non-genetic animal models for autism spectrum disorders (ASD) Reprod. Toxicol. 2016;64:116–140. doi: 10.1016/j.reprotox.2016.04.024. - DOI - PubMed

[9] Bhattacharya A., Kaphzan H., Alvarez-Dieppa A.C., Murphy J.P., Pierre P., Klann E. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron. 2012;76:325–337. doi: 10.1016/j.neuron.2012.07.022. - DOI - PMC - PubMed

[10] Bhattacharya A., Kaphzan H., Alvarez-Dieppa A.C., Murphy J.P., Pierre P., Klann E. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron. 2012;76:325–337. doi: 10.1016/j.neuron.2012.07.022. - DOI - PMC - PubMed

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Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

Affiliations

Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

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