MOTS-c · research summary

Therapeutic Effects of MOTS-c in the Valproic Acid-Induced Autism Model in Rats: Role of Tetrahydrobiopterin and Brain-Derived Neurotrophic Factor.

Molecular neurobiology · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Preclinical animal study using a valproic acid-induced rat model of autism
“To evaluate this hypothesis, we investigated the effects of MOTS-c in the valproic acid–induced rat model of autism.”

Subjects

Male and female Sprague-Dawley rats prenatally exposed to valproic acid or saline
“Pregnant Sprague-Dawley rats received intraperitoneal 500 mg/kg valproic acid or saline on embryonic day 12.”

Sample size

64 offspring rats (32 female and 32 male) divided into eight experimental groups
“In this study, 32 female and 32 male offspring rats, derived from 9 female Sprague-Dawley rats (RRID: RRRC_00239), were used.”

Duration

Treatment administered from postnatal day 21 to postnatal day 46
“Female and male offspring were treated with 0.5 mg/kg/day MOTS-c or saline intraperitoneally from postnatal days 21 to 46.”

Reported findings

MOTS-c treatment reversed VPA-induced impairments in sociability, repetitive behaviors, and cerebellar Purkinje cell loss
“These alterations were reversed by MOTS-c, except for anxiety and neocortical damage.”
MOTS-c reduced oxidative stress markers (MDA, T-SOD, T-GSH) in the prefrontal cortex
“MDA levels were lower in the F-VPA+MOTS-c group than in the F-VPA group (p = 0.005) and in the M-VPA+MOTS-c group than in the M-VPA group (p = 0.048).”
No significant changes were detected in plasma BH4 or BDNF levels
“No significant changes in plasma BH4 or BDNF levels were detected.”

Limitations stated by the authors

MOTS-c did not reverse anxiety-like behaviors or neocortical damage, and the peptide reportedly does not cross the blood-brain barrier
“These alterations were reversed by MOTS-c, except for anxiety and neocortical damage.”

Source: PubMed 41706383 · DOI 10.1007/s12035-026-05741-y · all study summaries

Reported findings

MOTS-c treatment reversed VPA-induced impairments in sociability, repetitive behaviors, and cerebellar Purkinje cell loss

“These alterations were reversed by MOTS-c, except for anxiety and neocortical damage.”

MOTS-c reduced oxidative stress markers (MDA, T-SOD, T-GSH) in the prefrontal cortex

“MDA levels were lower in the F-VPA+MOTS-c group than in the F-VPA group (p = 0.005) and in the M-VPA+MOTS-c group than in the M-VPA group (p = 0.048).”

No significant changes were detected in plasma BH4 or BDNF levels

“No significant changes in plasma BH4 or BDNF levels were detected.”