Glial fibrillary acidic protein and RNA expression in adult rat hippocampus following low-level lead exposure during development

Abstract

The astroglial cytoskeletal element, glial fibrillary acidic protein (GFAP), is a generally accepted sensitive indicator for neurotoxic effects in the mature brain. We used GFAP as a marker for structural changes in rat hippocampus related to chronic low level lead exposure during different developmental periods. Four groups of rats were investigated: a control group, a perinatal group, which was exposed during brain development (E0-P16), a permanent group, exposed during and after brain development (E0-P100), and a postweaning group, exposed after brain development (P16-P100). Sections were processed for light microscopy (hematoxylin-eosin, Nissl, periodic acid Schiff (PAS) and GFAP-specific immunohistology), for electron microscopy, and for in-situ hybridization (GFAP). Sections were prepared from animals tested for active avoidance learning (AAL) and long-term potentiation (LTP). Chronic lead exposure did not affect glial and neuronal functions, as assessed by LTP and AAL, when lead exposure started after brain development (postweaning group). In this group, astrocytes displayed increased GFAP and GFAP gene transcript levels. However, lead exposure affected neuronal and glial function when the intoxication fell into the developmental period of the brain (perinatal and permanent groups). In these groups, LTP and AAL were impaired, and astrocytes failed to react to the toxic exposure with an adequate increase of GFAP and GFAP gene transcripts. Although GFAP is an accepted marker for neurotoxicity, our data suggest the marker function of GFAP to be restricted to postnatal toxic insult.

Early-Life Lead Exposure Affects the Activity of TNF-α and Expression of SNARE Complex in Hippocampus of Mouse Pups

“…The nervous system is the primary target for the Pb exposure, and the developing brain appears to be especially vulnerable [24,25]. Pb exposure in the early stage of life may impair both glial and neuronal function [26,27]. The most important function of astroglial cells is maintenance of the homeostatic environment for proper functioning of neurons.…”

Behavioral deficits induced by lead exposure are accompanied by serotonergic and cholinergic alterations in the prefrontal cortex

“…Morris water maze task depend from hippocampus (Morris et al 1982) and related neuronal circuitry included prefrontal cortex which subserves attention and cognition (Leon et al 2010;Silachev et al 2009). Hippocampus is a brain area particularly sensitive to neurotoxic effect induced by postnatal Pb exposure since it induces astrogliosis (Selvin-Testa et al 1994, 1997, increases the expression of astrocyte marker glial-fibrillary acidic protein (GFAP) (Selvin-Testa et al 1994) or mRNA for GFAP (Stoltenburg-Didinger et al 1996) and increase myo-inositol concentration (Mansouri et al 2012). Alteration in hippocampus and prefrontal cortex (see later) might be at basis of impairment of learning and memory abilities induced by chronic lead exposure.…”

Age-Dependent Reductions in the Level of Glial Fibrillary Acidic Protein in the Prefrontal Cortex in Major Depression

“…For instance, low-level exposure of rat to lead at various developmental periods is associated with changes in levels of GFAP protein and mRNA in the adult hippocampus (Stoltenburg-Didinger et al, 1996). Exposure to lead after brain development results in increases in GFAP protein and mRNA.…”