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

*Corresponding author for this work

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 languageAmerican English
Pages (from-to)469-479
Number of pages11
JournalBehavioural Brain Research
Volume364
DOIs
StatePublished - 17 May 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

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

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