Beta-carotene as a novel therapy for the treatment of “Autistic like behavior” in animal models of Autism

Yosefa Avraham, Elliot M. Berry, Marina Donskoy, Wiessam Abu Ahmad, Lia Vorobiev, Amnon Albeck, David Mankuta

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Autism-affected individuals are characterized by lower plasma oxytocin and its ectoenzyme regulator CD38. Oxytocin, a hypothalamic hormone secreted upon the release of CD38, plays a role in social behavior and bonding. All-trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. We investigated the role of beta-carotene in rescuing autistic-like behavior in BALB/c and BTBR mice. Beta-carotene derivatives are preferred as they are neither toxic nor teratogenic. Beta-carotene at 0.1–5.0 mg/kg was administered orally to BALB/c and BTBR newborn mice on days 1–7. They were tested at age 2–3 months for five behavioral tests for “autism”; in addition, brain CD38, oxytocin, oxytocin receptor, Brain Derived Neurotrophic Factor (BDNF) and retinoic acid receptor gene expression, serum oxytocin levels, and neurological score were evaluated. Beta-carotene administered at birth significantly increased T-maze alternations and led to longer time spent with an unfamiliar mouse in the “three-chamber test” and less time spent in the empty chamber. Furthermore, enhanced activity in the open field test; increased time spent in the reciprocal social interaction test; decreased grooming and bedding behaviors; and enhanced brain CD38, oxytocin, oxytocin receptor, BDNF, retinoic acid gene expression, and serum oxytocin levels. No changes in neurological score were observed. Beta-carotene oral supplementation to BALB/c and BTBR mice at birth significantly reduced restricted and stereotyped behaviors and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity. Thus, beta-carotene administered after birth to newborns of families predisposed to “autism” has the potential to prevent/ameliorate” autistic like behavior”. These results support further clinical studies.

Original languageEnglish
Pages (from-to)469-479
Number of pages11
JournalBehavioural Brain Research
Volume364
DOIs
StatePublished - 17 May 2019

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.

Funding

We would like to thank the Israel Innovation Authority (Kamin Grant No. 53895 ) for their support, and especially for Dr Daphna Burowski, for her deep questions and review.

FundersFunder number
Israel Innovation Authority53895

    Keywords

    • Animal models
    • Autism
    • BDNF
    • Behavioral studies
    • Beta-carotene
    • Brain
    • CD38
    • Oxytocin
    • Retinoic acid receptor

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