Sex-dependent effects of imperatorin on autistic-like behaviors and BDNF signaling in rats prenatally exposed to valproic acid

IBRO Neurosci Rep. 2026 Oct 6;21:963-975. doi: 10.1016/j.ibneur.2026.09.022. eCollection 2026 Dec.

ABSTRACT

Autism spectrum disorder (ASD) is defined by cognitive impairments such as learning and memory decline, and social interaction and communication deficits. This study investigated the potential effects of Imperatorin (IMP), a furocoumarin and a phytochemical isolated from the leaves of Ferulago trifida on valproic acid (VPA)-induced behavioral and brain-derived neurotrophic factor (BDNF) alterations in a rat model of ASD. Open field test (locomotion, anxiety), grooming test, marble burying test (OCD-like behavior), novel object recognition memory test, and real-time PCR (BDNF levels) were conducted to collect data. The results showed increased locomotion in ASD-like rats in both sexes with greater effect in females, while IMP restored it in males and decreased it in females. Anxiety was increased in ASD-like rats in both sexes with greater effect in females; IMP had no effect. Grooming was increased in ASD-like rats in both sexes with greater effect in females, while IMP restored it in males and decreased it in females. Marbles buried was increased in ASD-like rats in both sexes, while IMP decreased it in males. Memory was impaired in ASD-like rats in both sexes; IMP had no effect. BDNF was decreased in ASD-like rats in both sexes with greater effect in females, while IMP increased it in both sexes. In conclusion, our findings showed hyperlocomotion, anxiety-like behavior, OCD-like behavior, memory deficit, and BDNF downregulation as ASD-related features, with evidence of sex-specific patterns and partial therapeutic effects of IMP.

PMID:42892986 | PMC:PMC13675637 | DOI:10.1016/j.ibneur.2026.09.022