Prenatal nicotine exposure affects hippocampal development and behavior in mouse offspring

To investigate the association between prenatal nicotine exposure (PNE) induced behavioral abnormalities in offspring and multiple classes of neuronal cell changes in the hippocampus at different developmental stages after birth, pregnant mice were injected subcutaneously with nicotine (1.5 mg/kg) from gestational day (GD) 9 until parturition. Multimodal histological analyses (Golgi staining, and immunohistochemistry) were performed on hippocampal DG, CA1, and CA3 regions at postnatal day (PD) 1, 7, 14, 21, and 90. Behavioral assessment (open field, tail suspension, forced swimming, sucrose preference, novel object recognition, and morris water maze tests) was conducted from PD56 to PD90. The results showed that PNE induced stage-specific alterations in hippocampal development, characterized by enhanced neuronal proliferation during early postnatal stages (PD1-7) and suppressed dendritic arborization during middle postnatal phases (PD14-21); persistent neurogenesis deficits were observed in the DG region, coupled with sustained reduction in dendritic spine density in CA1 pyramidal neurons throughout adulthood; the CA1 region demonstrated transient microglial depletion alongside persistent GABAergic interneuron deficiency; behavioral assessments revealed significant deficits in spatial learning and memory retention, as well as heightened anxiety- and depression-like phenotypes in adult PNE offspring.