The effects of chronic lead exposure on norepinephrinergic neurons of the nucleus locus ceruleus of the rat

Lee, Won Taek; Yoon, Ho; Lee, Dong Joo; Lee, Jong Eun; Koo, Chul Hoi; Park, Kyung Ah

Abstract

The neurotoxic effects of inorganic lead, a common environmental toxic substance, include peripheral neuropathy in adults and encephalopathy in children. Behavioral changes including hyperactivity, short attention span, easy distractibility and impulsiveness have also been noted in patients with chronic lead exposure in childhood. The level of norepinephrine in brain may relate to hyperactivity and chronic lead exposure. The purpose of this study was to determine the effect of inorganic lead (PbCl(2)) administration in neonatal rats using immunocytochemical and electron microscopical analysis of norepinephrinergic neurons of the locus ceruleus. Lead chloride were dissolved in distilled water at the concentration of 0.05%, 0.1% and 0.2% and the solution was administered orally via drinking water. After 4, 8 or 12 weeks of continuous administration, all rats were sacrificed and the brain was processed and immunostained with antibody against tyrosine hydroxylase, a rate limiting enzyme of norepinephrine synthesis antibody. The number of tyrosine hydroxylase immunostained cell bodies in locus ceruleus was estimated. Densitometric analysis of tyrosine hydroxylase immunoreactive profiles in electron microscopic photographs were done by using image analyzer. The number of tyrosine hydroxylase immunoreactive neurons in the locus ceruleus had increased statistically after lead administration. Density of tyrosine hydroxylase immunoreactive profiles in the electron microscopy had also increased. Degenerative changes, such as intra-axonal vacuolar space formation, were found within tyrosine hydroxylase immunoreactive axons. Somewhat widened intercellular spaces and retracted processes were also found in the region of the locus ceruleus. Increased tyrosine hydroxylase immunoreactivity may correlate with hyperreactivity of lead intoxicated children. Degenerative changes may be responsible for the short attention span, easy distractibility and impulsiveness observed in case of mild lead poisoning.