Perioperative pain-anxiety response profiles and their predictors in patients undergoing dental implant surgery: a latent profile analysis.

According to the newest estimates from the CDC (Centers for Disease Control and Prevention)’s ADDM (Autism and Developmental Disabilities Monitoring) Network (2025), 1 in 31 (3.2%) children aged 8 years have been diagnosed with autism spectrum disorder (ASD) (surveillance year 2022). Human neuroimaging studies from ASD patients showed differences in brain morphology, function, and circuits connectivity in males and females (), which may underlie the heterogeneity of phenotypic manifestations in males and females. However, the potential neural mechanisms underlying the sex differences in ASD remain a significant gap (). ASD is caused by genetic mutations and/or exposure to environmental factors (Simons Foundation Autism Research Initiative, SFARI) (; ; ; ; ; ; ; ). We and others believe that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in patients with ASD (; ). Given the critical role of activity-dependent brain-derived neurotrophic factor (BDNF) signaling in the brain, the impact of diminished activity-dependent BDNF signaling on social deficits in males and females by using mice with genetic knock-in of this human BDNF methionine (Met) allele was examined, which significantly reduced up to 30% of activity-dependent BDNF release without affecting basal BDNF secretion (; ). Diminished activity-dependent BDNF signaling caused differential severity of autism-like social preference deficits in male and female mice, and male mice appeared to be more severe than females (). Growing evidence suggests that elevated excitatory/inhibitory (E/I) balance in the PFC is a major pathogenesis of social deficits in animal autistic mouse models and ASD patients (; ; ). Pyramidal neurons are the principal neurons in the prefrontal cortex (PFC), a critical brain region for social behavior (; ; ), which are impaired in patients with ASD (). Activity-dependent BDNF signaling plays critical roles in cognition via the homeostatic regulation of neuronal intrinsic properties and synaptic transmission (; ; ). The diminished activity-dependent BDNF signaling increased intrinsic excitability of pyramidal neurons in male BDNF mice, but not in female BDNF mice, via increased expression of (encodes sodium channel Nav1.2) and decreased expression of (encodes small-conductance calcium-activated potassium channel 2, SK2) (), which decreased the thresholds of action potentials and facilitated the propagation of firing (; ; ). The increased intrinsic excitability of pyramidal neurons in the PFC might partially contribute to social preference deficits in male BDNF mice. However, the neural mechanisms that contribute to social preference deficits in female BDNF mice are unknown. The driving force for neuronal excitability is derived from intrinsic membrane properties (permissive gate) and synaptic inputs (). In this study, we examined the impact of activity-dependent BDNF signaling on the synaptic transmission of pyramidal neurons in the PFC to reveal the potential neural mechanisms underlying the differential severity of social preference deficit in male and female BDNF mice.