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 (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.

Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats

“…For instance, beta‐actin mRNA levels are expressed less in aged rats (Nishibayashi et al, ). In addition, exposure to lead (Pb 2+ ) enhanced NO production and reduced the expression of synaptic synatophysin and synaptobrevin (Neal et al, ), which are proteins involved in vesicular release and recycling (for review see Gordon and Cousin, ).…”

“…For instance, beta-actin mRNA levels are expressed less in aged rats (Nishibayashi et al, 1994). In addition, exposure to lead (Pb 21 ) enhanced NO production and reduced the expression of synaptic synatophysin and synaptobrevin (Neal et al, 2012), which are proteins involved in vesicular release and recycling (for review see Gordon and Cousin, 2013). However, the mechanisms by which Cbl enhanced the cognitive and dendritic arbor and dendritic spines of the PFC and hippocampus in SH rats are unknown.…”

Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1

“…Interestingly, NO in the hippocampus is a key molecule implicated in the regulation of the synaptic communication (for review see Cossenza et al, ; Hardingham et al, ; Hu and Zhu, ). For example, exposure to Pb 2+ enhanced NO production and reduced expression of synaptic synatophysin (Syn) and synaptobrevin (Syb) (Neal et al, ), proteins involved in the vesicular release and recycling (for review see Gordon and Cousin, ). This exocytotic process is involved in the synaptic communication (for review see Shin, ).…”

Sex-dependent effects of lead and prenatal stress on post-translational histone modifications in frontal cortex and hippocampus in the early postnatal brain

“…It is possible that an interaction between genes and sex hormones during development may make a variety of brain regions, including the frontal cortex and hippocampus, which are particularly sensitive to the effects of Pb and PS (Cory-Slechta et al, 1998; Cory-Slechta et al, 1999; Berger et al, 2002; Barros et al, 2004; Virgolini et al, 2008a; Martinez-Tellez et al, 2009; Rossi-George et al, 2011; Neal et al, 2012; Stansfield et al, 2012; Baranowska-Bosiacka et al, 2013; Hu et al, 2014; Li et al, 2014; Li et al, 2015), and differentially susceptible to epigenetic alterations, such as post-translational histone modifications, that are associated with modulation of transcriptional regulation.…”