Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation.
Neuroscience
; 558: 92-104, 2024 Oct 18.
Article
in En
| MEDLINE
| ID: mdl-39168175
ABSTRACT
This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylcarnitine
/
Autistic Disorder
/
Valproic Acid
/
Oxidative Stress
/
Hippocampus
/
Mitochondria
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Neuroscience
Year:
2024
Document type:
Article
Affiliation country:
Iran
Country of publication:
United States