Effects of Postnatally Administered Inorganic Lead on the Tyrosine Hydroxylase Immunoreactive Norepinephrinergic Neurons of the Locus Ceruleus of the Rat.

Abstract

The neurotoxic effects of inorganic lead are known to include peripheral neuropathy in adults and encephalopathy in children. The purpose of this study was to determine the effect of inorganic lead (PbCl2) administration on norepinephrinergic neurons of the locus ceruleus in neonatal rats by immunocytochemical and electron microscopic analyses. Lead chloride solutions, 0.05%, 0.1% and 0.2% in concentrations, were prepared in distilled water and administered orally via drinking water. After 4, 8, or 12 weeks of continuous administration, the rats were sacrificed and brains were immunostained with the tyrosine hydroxylase antibody. The number of immunoreactive cell bodies in the locus ceruleus was estimated. Densitometric analysis of immunoreactive profiles visualized by electron microscopy was performed using an image analyzer. The numbers of immunoreactive neurons in the locus ceruleus were increased statistically by lead administration. The intensity of the immunoreaction, both under the light and electron microscopes was also increased. Degenerative changes, including intra-axonal vacuole formation and widening of the extracellular spaces, were found by electron microscopy in and around the tyrosine hydroxylase immunoreactive axons. Increased tyrosine hydroxylase immunoreactivity may correlate with the hyper-reactivity of lead intoxicated children. Degenerative changes may account for the reported deficits in intellectual attainment and achievement in lead intoxicated children.

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“…Thus, the offspring were consistently exposed to lead (or not) from the day of their mother's insemination until the start of their own periadolescence (Spear & Brake, 1983). The numerous studies using developmental exposure to 0.1% lead in laboratory rats show it produces a range of ∼10–15 μg/dL lead in the mothers during treatment (Sant'Ana et al., 2001), ∼30–60 μg/dL lead in neonates and young pups suckling lead‐treated dams (McGivern et al., 1991; Michaelson & Bradbury, 1982), and up to ∼70 μg/dL in weanlings that themselves are drinking the leaded water (Hejtmancik et al., 1982; Lee et al., 2002; Moorhouse et al., 1988). 0.1% lead acetate is considered a lower dose in experimental studies of laboratory rodents, but the U.S. Centers for Disease Control and Prevention states that children's blood lead levels >3.5 μg/dL is of concern, which represents the levels found in the top 2.5% of 1–5 year olds (Zuch et al., 1998).…”