Prenatal heat stress is an important environmental risk factor for offspring neurodevelopmental disorders, but effective interventions remain limited. In this study, pregnant mice were exposed to heat stress (42 °C, 15 min) per day from gestational days 10.5 to 18.5 and treated with BHBA (200 mg/(kg·d)). Behavioral tests, including the open field test, elevated plus maze, and Morris water maze, were combined with BrdU/GFAP/NeuN immunofluorescence, transcriptome sequencing, and Golgi staining to evaluate the effects of BHBA on offspring neurobehavior. BHBA significantly improved anxiety-like behavior and spatial learning and memory deficits in heat-stressed offspring, and these protective effects persisted into adulthood. Mechanistically, BHBA promoted neural stem cell differentiation toward neurons, suppressed excessive glial proliferation, and reversed deficits in adult hippocampal neurogenesis. It also inhibited overactivation of hippocampal dopaminergic synapses, reduced Drd1, Drd2, and TH expression, and restored dendritic spine maturation and synaptic plasticity. This work provides a potential nutritional intervention strategy and translational research framework for neurodevelopmental disorders associated with early-life environmental stress.
The work entitled “Mechanism of β-hydroxybutyrate-mediated improvement in social behavior deficits of heat-stressed offspring” was published on Journal of Shanxi Agricultural University (Natural Science Edition) (published on August 31, 2026).
DOI: 10.13842/j.cnki.issn1671-8151.202602015