Chronic low‐level lead exposure affects the monoaminergic system in the mouse superior olivary complex

Abstract

Low-level lead (Pb) exposure is associated with behavioral and cognitive dysfunction but it is not clear how Pb produces these behavioral changes. Pb has been shown to alter auditory temporal processing in both humans and animals. Auditory temporal processing occurs in the superior olivary complex (SOC) in the brainstem where it is an important component in sound detection in noisy environments and in selective auditory attention. The SOC receives a serotonergic innervation from the dorsal raphe, and serotonin has been implicated in auditory temporal processing within the brainstem and inferior colliculus. Because Pb exposure modulates auditory temporal processing, the serotonergic system is a potential target for Pb. The current study was undertaken to determine whether developmental Pb exposure preferentially changes the serotonergic system within the SOC. Pb-treated mice were exposed to no Pb, very low Pb (0.01 mM), or low Pb (0.1 mM) throughout gestation and through 21 days postnatally. Brainstem sections from control and Pb-exposed mice were immunostained for the vesicular monoamine transporter 2 (VMAT2), serotonin, and dopamine beta hydroxylase (DβH, a marker for norepinephrine) in order to elucidate the effect of Pb on monoaminergic input into the SOC. Sections were also immunolabeled with antibodies to VGLUT1, VGAT and VAChT to determine whether Pb exposure alters the glutaminergic, gaba-ergic, or cholinergic systems. Pb exposure caused a significant decrease in VMAT2, 5HT, and DβH expression while VGLUT1, VGAT and VAChT showed no change. These results provide evidence that Pb exposure during development alters normal monoaminergic expression in the auditory brainstem.

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss

“…Blood lead levels ≥2 μg/dl, which is well below the current action level (5 μg/dl) recommended by the Centers for Disease Control and Prevention (CDC advisory committee report, 2012), were associated with higher odds of high-frequency hearing loss (Shargorodsky et al, 2011). Exposure to low levels of lead during development decreased the expression of voltage-dependent anion channel proteins and disrupted the monoaminergic system in the auditory brainstem (Fortune and Lurie, 2009; Prins et al, 2010a,b). Furthermore, lead exposure induced degeneration of sensory receptor cells in the cochlea, affected auditory nerve conduction velocity, disrupted cochlear blood-labyrinth barrier, and caused vestibular dysfunction (Jones et al, 2008; Klimpel et al, 2017; Lasky et al, 1995; Liu et al, 2013; Yamamura et al, 1989).…”

Organization of the Serotonergic System in the Central Nervous System of Two Basal Actinopterygian Fishes: the Cladistians <b><i>Polypterus senegalus</i></b> and <b><i>Erpetoichthys calabaricus</i></b>

“…According to the data sheet: (1) positive staining is obtained in rat raphe nuclei and spinal cord [see also Fortune and Lurie, 2009;Alonso et al, 2013]; (2) the antiserum diluted 1:20,000 does not react with 5-, 10-, and 25-μg amounts of 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, and dopamine using the BSA/HRP labeling method, and (3) pretreatment of the diluted antiserum with 25 μg of serotonin coupled to BSA completely eliminates the staining. In addition, we verified the specificity of the immunoreaction in cladistians by preadsorbing the primary antibody with the serotonin-BSA conjugate used for generation of the antiserum (serotonin creatinine sulfate coupled to BSA with paraformaldehyde, catalog No.…”

Lead Exposure in Different Organs of Mammals and Prevention by Curcumin–Nanocurcumin: a Review

“…Binding to their sulfhydryl groups can also inflect protein activity of many proteins and can inhibit the expression of antioxidant enzymes such as SOD and catalase [39]. Lead neurotoxicity has been investigated and caused by mixture of mechanisms like disruption of neurotransmitter systems [40]. GABA is the primary inhibitory neurotransmitter in the adult CNS.…”