Beta-carotene as a novel therapy for the treatment of "Autistic like behavior" in animal models of Autism.
ADP-ribosyl Cyclase 1
/ metabolism
Animals
Animals, Newborn
Autism Spectrum Disorder
/ drug therapy
Autistic Disorder
/ drug therapy
Behavior, Animal
/ drug effects
Brain-Derived Neurotrophic Factor
/ metabolism
Disease Models, Animal
Female
Interpersonal Relations
Male
Membrane Glycoproteins
/ metabolism
Mice
Mice, Inbred BALB C
Oxytocin
/ metabolism
Receptors, Retinoic Acid
/ metabolism
Social Behavior
beta Carotene
/ metabolism
Animal models
Autism
BDNF
Behavioral studies
Beta-carotene
Brain
CD38
Oxytocin
Retinoic acid receptor
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
17 05 2019
17 05 2019
Historique:
received:
04
07
2017
revised:
14
09
2017
accepted:
25
09
2017
pubmed:
1
10
2017
medline:
14
2
2020
entrez:
1
10
2017
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 28963040
pii: S0166-4328(17)31103-8
doi: 10.1016/j.bbr.2017.09.041
pii:
doi:
Substances chimiques
Bdnf protein, mouse
0
Brain-Derived Neurotrophic Factor
0
Membrane Glycoproteins
0
Receptors, Retinoic Acid
0
beta Carotene
01YAE03M7J
Oxytocin
50-56-6
Cd38 protein, mouse
EC 3.2.2.5
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
469-479Informations de copyright
Copyright © 2017 Elsevier B.V. All rights reserved.