Independent and combined effects of astaxanthin and omega-3 on behavioral deficits and molecular changes in a prenatal valproic acid model of autism in rats

ABSTRACT

Objectives: Autism is a devastating neurodevelopmental disorder and recent studies showed that omega-3 or astaxanthin might reduce autistic symptoms due to their anti-inflammatory properties. Therefore, we investigated the effects of omega-3 and astaxanthin on the VPA-induced autism model of rats.

Material and Methods: Female Wistar albino pups (n = 40) were grouped as control, autistic, astaxanthin (2 mg/kg), omega-3 (200 mg/kg), and astaxanthin (2 mg/kg)+omega-3 (200 mg/kg). All groups except the control were prenatally exposed to VPA. Astaxanthin and omega-3 were orally administered from the postnatal day 41 to 68 and behavioral tests were performed between day 69 and 73. The rats were decapitated 24 h after the behavioral tests and hippocampal and prefrontal cytokines and 5-HT levels were analyzed by ELISA.

Results: VPA rats have increased grooming behavior while decreased sociability (SI), social preference index (SPI), discrimination index (DI), and prepulse inhibition (PPI) compared to control. Additionally, IL-1β, IL-6, TNF-α, and IFN-γ levels increased while IL-10 and 5-HT levels decreased in both brain regions. Astaxanthin treatment raised SI, SPI, DI, PPI, and prefrontal IL-10 levels. It also raised 5-HT levels and decreased IL-6 levels in both brain regions. Omega-3 and astaxanthin + omega-3 increased the SI, SPI, DI, and PPI and decreased grooming behavior. Moreover, they increased IL-10 and 5-HT levels whereas decreased IL-1β, IL-6, TNF-α, IFN-γ levels in both brain regions.

Conclusions: Our results showed that VPA administration mimicked the behavioral and molecular changes of autism in rats. Single and combined administration of astaxanthin and omega-3 improved the autistic-like behavioral and molecular changes in the VPA model of rats.

GRAPHICAL ABSTRACT

KEYWORDS:

• Autism
• Valproic acid
• Repetitive behaviors
• Social interaction
• Prepulse inhibition
• Neuroinflammation
• Novel object recognition
• Omega-3
• Astaxanthin

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement (DAS)

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Emre Adiguzel

Emre Adıgüzel (16 publications) is currently an Asst. Prof. in the Department of Nutrition and Dietetics at Karamanoğlu Mehmetbey University and has studies on the gut-brain axis in autism spectrum disorder (ASD).

Nuh Mehmet Bozkurt

Nuh Mehmet Bozkurt (4 publications), a Res. Asst. in the Department of Pharmacology at Erciyes University, studies the effects of some active ingredients on impaired social interaction and startle reflex in experimental schizophrenia models.

Gokhan Unal

Gökhan Ünal (30 publications), an Assoc. Prof. in the Department of Pharmacology at Erciyes University, has studies on social and cognitive deficits of psychiatric diseases in experimental models of rodents.