| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4325450 | Brain Research | 2012 | 8 Pages |
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 +.
