title: Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading, and temporal processing deficits within the murine auditory brainstem.
abstract: Low-level lead (Pb) exposure is a risk factor for learning disabilities, attention deficit hyperactivity disorder (ADHD), and other neurological dysfunction. It is not known how Pb produces these behavioral deficits, but low-level exposure during development is associated with auditory temporal processing deficits in an avian model, while hearing thresholds remain normal. Similar auditory processing deficits are found in children with learning disabilities and ADHD. To identify cellular changes underlying this functional deficit, Pb-induced alterations of neurons and glia within the mammalian auditory brainstem nuclei were quantified in control and Pb-exposed mice at postnatal day 21 by using immunohistochemistry, Western blotting, and 2D gel electrophoresis. Pb-treated mice were exposed to either 0.1 mM (low) or 2 mM (high) Pb acetate throughout gestation and through 21 days postnatally. Pb exposure results in little change in glial proteins such as glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), or F4/80 as determined by Western blot analysis and immunohistochemistry. In contrast, Pb exposure alters neuronal structural proteins by inducing increased phosphorylation of both the medium (NFM) and high-weight (NFH) forms of neurofilament within auditory brainstem nuclei. Axons immunolabeled for neurofilament protein show neuritic beading following Pb exposure both in vivo and in vitro, suggesting that Pb exposure also impairs axonal transport. Functional assessment shows no significant loss of peripheral function, but does reveal impairments in brainstem conduction time and temporal processing within the brainstem. These results provide evidence that Pb exposure during development alters axonal structure and function within brainstem auditory nuclei.
authors: Center for Environmental Health Sciences, The University of Montana, Missoula, Montana 59812, USA.
authors: Linda G
authors: LG
authors: Jones
authors: John
authors: J
authors: Prins
authors: Sunyoung
authors: S
authors: Park
authors: Joseph P
authors: JP
authors: Walton
authors: Anne E
authors: AE
authors: Luebke
authors: Diana I
authors: DI
authors: Lurie
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D002452:Cell Count; D002461:Cell Line, Transformed; D015180:Electrophoresis, Gel, Two-Dimensional; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D011897:Random Allocation; D011930:Reaction Time / Q000528:radiation effects
chemical_list: D000943:Antigens, Differentiation; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; C036763:monocyte-macrophage differentiation antigen; D007854:Lead