Developmental exposure to lead interferes with glial and neuronal differential gene expression in the rat cerebellum.
Exposure to lead (Pb) has been shown to disrupt developmental processes in the brain and to result in impaired brain function. In these studies, we examined the role of differential gene expression as a possible target site which may partially mediate Pb's neurotoxicity. Animals were lactationally exposed to 0.2% lead acetate from birth to weaning. On postnatal days (PND) 3, 6, 9, 12, 15, 20, 25, 30, 40, and 50, the cerebelli of control and Pb-exposed pups were examined, by Northern blot analysis for changes in the developmental profiles of neuronotypic and gliotypic markers: Growth-associated protein (GAP-43), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP), while actin was monitored as an indicator of generalized effects on developmental gene expression and exhibited no significant changes following Pb exposure. On PND 9, Pb exposure resulted in a significant stimulation in the expression of the neuronal GAP-43 mRNA. Although Pb induced an early onset of MBP gene expression, the mRNA levels for both MBP and GFAP were decreased between PND 20 and 50, in Pb-exposed animals. These studies suggest that exposure to Pb may selectively interfere with critical developmental gene expression.
Zawia
N H
NH
Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Harry
G J
GJ
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D019922:GAP-43 Protein; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D007854:Lead / Q000633:toxicity*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
D000199:Actins; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007854:Lead