Year of Award

2007

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Toxicology

Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Chair

Diana Lurie

Keywords

auditory brainstem, lead, monoamines, vesicle synaptophysin, vmat

Abstract

Low-level lead (Pb) exposure is associated with behavioral and cognitive dysfunction. It is not clear how Pb produces these behavioral changes but low-level Pb exposure and learning disabilities have been associated with altered auditory temporal processing in both humans and animals. Temporal processing is used to decode complex sounds and to detect a signal within a noise background, and it is thought that neurons of the superior olivary complex (SOC) in the brainstem play a role in sound detection in noisy environments and in selective auditory attention. The SOC receives a catecholaminergic and a serotonergic innervation from the locus coeruleus and the dorsal raphe respectively. While the physiological role of the noradrenergic input has yet to be defined, serotonin is involved in auditory temporal processing. 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 expression of serotonin within the SOC. Pb-treated mice were exposed to no Pb, 0.01 mM (very low) or 0.1 mM (Low) Pb acetate 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. In addition, sections were immunolabeled with antibodies to VGLUT1, VGAT and VAChT in order 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.

Download

Share

COinS
 

© Copyright 2007 Tyler John Fortune