title: Effects of Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development on spatial learning and memory.
abstract: The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. Chronic exposure to lead (Pb2+) causes deficits of learning and memory in children and spatial learning deficits in developing rats. Brn-3a is a member of the Pit-Oct-Unc (POU) family of transcription factors that is expressed predominantly in neuronal cells. It exists in two forms, with the long form containing 84 amino acids at the N-terminus that are lacking in the short form. The N-terminal domain unique to the long form induces expression of the Bcl-2 gene and protects neuronal cells against apoptosis whereas the C-terminal POU domain common to both forms is sufficient for activating a number of other neuronally expressed genes and stimulating neuronal process outgrowth. We examined Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development and subsequent effects on spatial learning and memory. Two groups of rats were investigated: a control group and a lead-exposed group (0.2% lead acetate in the drinking water of the dam from gestational day 15 to postnatal day 21). Levels of Brn-3a were measured in rat cortex, hippocampus and cerebellum by immunohistochemistry and in situ hybridization, both protein and mRNA levels were reduced in lead-exposed group (p < 0.05). In Morris water maze, we found spatial learning deficits in rats of lead-exposed group (p < 0.05). These data suggest that the alteration of Brn-3a may play a key role in the mechanisms underlying lead neurotoxicity.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huanzhong University of Science and Technology, Wuhan, Huibei 430030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qing-yi
authors.initials: QY
authors.lastname: Wei
authors.forename: Xue-min
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007854:Lead / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects; D050819:Transcription Factor Brn-3A / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D050819:Transcription Factor Brn-3A; D007854:Lead