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Psychiatry Clin Neurosci. 2019 Jun;73(6):317-322. doi: 10.1111/pcn.12833. Epub 2019 Apr 1.

Betaine ameliorates prenatal valproic-acid-induced autism-like behavioral abnormalities in mice by promoting homocysteine metabolism.

Author information

1
Psychiatric Ward, Qingdao Mental Health Center, Qingdao, China.
2
Psychological Clinic, Affiliated Hospital of Qingdao University, Qingdao, China.
3
Psychosomatic Ward, Shandong Mental Health Center, Jinan, China.

Abstract

AIM:

Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder. Betaine is a methyl group donor in Hcy metabolism, and is known to prevent noxious Hcy accumulation. This study explored whether betaine could influence Hcy metabolism in a mouse model of autism and ameliorate behavioral abnormalities.

METHODS:

Pregnant ICR mice were administered valproic acid (VPA) intraperitoneally on Embryonic Day 12.5. Serum Hcy concentrations in the offspring were measured by enzyme-linked immunosorbent assay. Expressions of Hcy-metabolism-related enzymes, betaine-Hcy methyltransferase, cystathionine β-synthase, and methionine synthase, were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Offspring were treated by either betaine or saline at the age of 8 weeks and serum Hcy concentrations were measured. Social behaviors were assessed by sniff-duration test and three-chamber test. Repetitive behavior was evaluated by marble-burying test. Tail-flick test was performed to measure nociceptive sensitivity.

RESULTS:

Prenatal VPA-exposed mice showed significantly elevated Hcy concentrations and decreased betaine-Hcy methyltransferase expression. Treatment with betaine could reduce Hcy level in VPA-exposed mice, attenuate social impairment and repetitive behavior, and normalize nociceptive sensitivity in this model.

CONCLUSION:

Betaine could ameliorate autism-like features and play a beneficial role in a mouse autism model induced by prenatal VPA exposure.

KEYWORDS:

autism; behavior; betaine; homocysteine; valproic acid

PMID:
30821067
DOI:
10.1111/pcn.12833

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