title: 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 (5-HT), and dopamine-beta-hydroxylase (DbetaH; 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 vesicular glutamate transporter 1 (VGLUT1), vesicular gamma-aminobutyric acid (GABA) transporter (VGAT), and vesicular acetylcholine transporter (VAChT) to determine whether Pb exposure alters the glutaminergic, GABAergic, or cholinergic systems. Pb exposure caused a significant decrease in VMAT2, 5-HT, and DbetaH expression, whereas VGLUT1, VGAT, and VAChT showed no change. These results provide evidence that Pb exposure during development alters normal monoaminergic expression in the auditory brainstem.
authors.affiliation: Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, The University of Montana, Missoula, Montana 59812-1552, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Fortune
authors.forename: Diana I
authors.initials: DI
authors.lastname: Lurie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001933:Brain Stem; D002452:Cell Count; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007245:Inferior Colliculi / Q000166:cytology / Q000187:drug effects; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D009847:Olivary Nucleus / Q000166:cytology / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D050494:Vesicular Acetylcholine Transport Proteins; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C492244:Viaat protein, mouse; D007854:Lead; D012701:Serotonin; D004299:Dopamine beta-Hydroxylase