Enhanced nitric oxide production during lead (Pb2 +) exposure recovers protein expression but not presynaptic localization of synaptic proteins in developing hippocampal neurons

We have previously reported that lead (Pb2 +) exposure results in both presynaptic and postsynaptic changes in developing neurons as a result of inhibition of the N-methyl-d-aspartate receptor (NMDAR). NMDAR inhibition by Pb2 + during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb2 + on both presynaptic protein expression and presynaptic vesicular release. NMDAR activity can modulate other trans-synaptic signaling pathways, such as nitric oxide (NO) signaling. Thus, it is possible that other trans-synaptic pathways in addition to BDNF signaling may be disrupted by Pb2 + exposure. The current study investigated whether exogenous addition of NO could recover the presynaptic vesicular proteins lost as a result of Pb2 + exposure during synaptogenesis, namely Synaptophysin (Syn) and Synaptobrevin (Syb). We observed that exogenous addition of NO during Pb2 + exposure results in complete recovery of whole-cell Syn levels and partial recovery of Syn and Syb synaptic targeting in Pb2 +-exposed neurons.

► Pb2 + reduces cellular Synaptophysin levels and synaptic targeting of presynaptic proteins.
► Previous work showed that Pb2 + can disrupt NMDAR dependent trans-synaptic signaling.
► Supplementation with NO during Pb2 + exposure fully rescued Syn whole cell expression.
► NO supplementation did not recover Pb2 + effects on synaptic protein localization.
► Thus NO recovers deficits in cellular but not synaptic protein expression due to Pb2 +.