Early postnatal tobacco smoke exposure triggers anxiety-like behavior and decreases synaptic proteins even after a long exposure-free period in mice

Although environmental tobacco smoke (ETS) is mainly associated to cardiorespiratory disease, clinical and preclinical studies have showed that ETS induces behavioral disorders and deleterious effects in the brain. Our aim was to investigate the effects of ETS during the early postnatal period on locomotor activity and anxiety and in the presynaptic proteins and brain-derived neurotrophic factor (BDNF) in distinct brain regions. BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes from the third to the fourteenth days of life. Behavioral and biochemical analyzes were performed during infancy, adolescence, and adulthood. ETS exposure induced a decrease in the locomotor activity in both female and male mice during infancy and in male mice during adolescence. Mice exposed to ETS showed lower distance traveled in the open arms of the elevated plus maze than control group. We also observed a decrease in synapsin levels in the cerebellum and striatum during infancy and adolescence, which persisted during the adulthood only in the cerebellum. Synaptophysin levels were low in all brain regions studied during the infancy, which remained reduced in the cerebellum and prefrontal cortex during adolescence and in the prefrontal cortex during adulthood. BDNF levels were reduced in the striatum and prefrontal cortex during infancy. These behavioral and biochemical data indicate that exposure to ETS during a critical development period leads to anxiety-like behavior and blunted synaptic proteins levels in different regions of the brain. More important, several of these effects were not reversed even after a long exposure-free period.