LEAD-INDUCED ALTERATIONS OF GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) INTHE DEVELOPING RAT-BRAIN

The developing nervous system is preferentially vulnerable to lead exp osure with alterations in neuronal and glial cells of the brain. The p resent study examined early lead-induced alterations in the developing astrocyte population by examination of the developmentally regulated astrocyte specific protein, glial fibrillary acidic protein (GFAP). A developmental profile (Postnatal Day (PND) 6, 9, 12, 15, 20, and 25) f or GFAP mRNA was generated for the cortex and hippocampus of developin g Long-Evans hooded male rats under various lead exposure conditions: (1) prenatal (Gestational Day 13 to birth), (2) postnatal (Postnatal D ay 1 to Postnatal Day 20), or (3) perinatal (Gestational Day 13 to Pos tnatal Day 20) exposure to lead acetate (0.2% in the drinking water of the dam). Control GFAP mRNA levels displayed a developmentally regula ted profile of expression. In the cortex this was characterized by a t ransient elevation in peak level between PND 9 and PND 15 followed by a decline to within adult levels by PND 25. Under all lead acetate exp osure conditions, the cortex showed an increase in the peak level of e xpression and extended the time of elevation of GFAP mRNA until PND 20 . Levels of GFAP were elevated at PND 60 but not as early as PND 28. I n the control hippocampus, levels of GFAP mRNA gradually increased unt il PND 20 followed by a sharp decline at PND 25. Postnatal and perinat al lead exposure followed a similar pattern; however, levels declined earlier at PND 20. Following prenatal lead exposure, levels of GFAP mR NA showed an earlier peak at PND 12 and a decrease as early as PND 15. By PND 60 protein level for GFAP was elevated in the postnatal lead e xposure group only. As demonstrated by GFAP immunoreactivity, these le ad-induced elevations were not associated with astrocyte hypertrophy. Following a physical injury in the cortex, astrocyte reactivity was si milar between lead-exposed and control rats. These data suggest an alt eration in the timing of astrocyte differentiation and maturation in t he brain following developmental lead exposure. (C) 1996 Academic Pres s, Inc.