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Lead (Pb) exposure is well-known to impair synaptic transmission and input-specific synaptic plasticity (LTP, LTD) in developing hippocampus.But whether lead affects the synapse formation and homeostatic synaptic plasticity remains elucidated.Our recent work showed lead exposure during synaptogenesis alters Wnt signals expression and thus affects the dendritic spine formation and synapse strength.To investigate the alteration of spine formation, Golgi-Cox staining method was used to analyze the spine density of pyramidal neurons in hippocampus (CA1) of P14 and P21 rats, which received Pb2+ from milk of dams.The results showed that Pb2+ obviously down-regulated the spine density in these two critical time points.The western blot results showed that there was also a significant age-related decline of the Wnt7a expression and its downstream protein stability after chronically lead exposure.In the cultured hippocampal neurons, Pb2+ significantly decreased the spine density in a dose-dependent manner.After exogenous Wnt7a application, the frequency of miniature excitatory postsynaptic currents (mEPSCs) in the Pb2+-treated group was rescued.Additionally, Pb2+-induced decrease of spine density was attenuated by Wnt7a, accompanying with the increasing of molecular stability in the Wnt pathway.Our results suggest that Pb2+ induced deficit in spine growth and synaptic transmission of developing hippocampus involving presynaptic Wnt7a signaling alteration.