title: Enhanced nitric oxide production during lead (Pb²⁺) exposure recovers protein expression but not presynaptic localization of synaptic proteins in developing hippocampal neurons.
abstract: We have previously reported that lead (Pb(2+)) 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 Pb(2+) during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb(2+) 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 Pb(2+) exposure. The current study investigated whether exogenous addition of NO could recover the presynaptic vesicular proteins lost as a result of Pb(2+) exposure during synaptogenesis, namely Synaptophysin (Syn) and Synaptobrevin (Syb). We observed that exogenous addition of NO during Pb(2+) exposure results in complete recovery of whole-cell Syn levels and partial recovery of Syn and Syb synaptic targeting in Pb(2+)-exposed neurons.
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. april.neal@fda.hhs.gov
authors.forename: April P
authors.initials: AP
authors.lastname: Neal
authors.forename: Kirstie H
authors.initials: KH
authors.lastname: Stansfield
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D009924:Organ Culture Techniques; D050683:R-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016708:Synaptophysin; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D050683:R-SNARE Proteins; D016708:Synaptophysin; C569016:Syp protein, rat; D033921:Vesicular Transport Proteins; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D007854:Lead; D009569:Nitric Oxide