Cuminaldehyde, a Hopeful Agent, Mitigates Autistic-Like Behaviors, Combating Hippocampal Neuroinflammation in Maternal Separation Stress Model in Male Mice

Background and aim

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that appears in the earliest ages of the lifespan. The causes of ASD remain anonymous, although immunological, genetic, biological, and psychosocial theories have been proposed. Stresses during early life, such as maternal separation (MS), are one of the psychosocial causes of ASD. The neuroimmune response is complicated in the pathophysiology of ASD. Cuminaldehyde (CA) has different pharmacological effects, such as anti-inflammatory properties. This study aimed to explore effects of CA on autistic-like behaviors in maternally separated mice with respect to its probable anti-neuroinflammatory effects.

Methods

Forty male mice were randomly allocated to five groups, including control mice administered with normal saline, and MS groups received normal saline and CA with doses of 5, 25, 50 mg/kg intraperitoneally for 14 continuous days. The three-chamber sociability, the resident–intruder, and shuttle box tests were performed. Subsequently, mice were euthanized, and the expression of the NLRP3, TLR4, HMGB1, and IL-1β genes in the hippocampus was investigated using real-time PCR.

Results

MS mice showed diminished sociability preference, damaged passive avoidance memory, as well as aggressive behaviors. Behaviors related to autism in MS mice are associated with a rise in the expression of inflammatory markers in the hippocampus. CA reversed the deleterious effects of MS on behaviors, in addition to a decrease in the expression of inflammatory genes in the hippocampus.

Conclusion

CA, via attenuation of neuroimmune reaction in the hippocampus, partially mitigated autistic-like behaviors in the MS mouse model.