Effects of Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development on spatial learning and memory.

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.