Effect of Chronic Lead Ingestion by Rats on Glucose Metabolism and Acetylcholine Synthesis in Cerebral Cortex Slices

Abstract

The effect of chronic low-level lead (Pb2+) ingestion on the metabolic pathways leading to the acetyl moiety of acetylcholine (ACh) was examined. Cerebral cortex slices, prepared from untreated or Pb2+-exposed rats (600 ppm lead acetate in the drinking water for 20 days), were incubated in Krebs-Ringer bicarbonate buffer with 10 mM glucose and tracer amounts of [6-3H]glucose and either [6-14C]glucose or [3-14C] beta-hydroxybutyrate. Altering the concentration of Pb2+ in the drinking water produced a dose-related increase in blood and brain lead levels. When tissue from Pb2+-exposed rats was incubated with mixed-label glucose, incorporation into lacate, citrate, and ACh was considerably decreased, although no changes occurred in the 3H/14C rations. Similar effects of Pb2+ were found when 14C-labeled beta-hydroxybutyrate was substituted for the [14C]glucose. It appears from these data that Pb2+ exerts a generalized effect on energy metabolism and not on a specific step in glucose metabolism. The impairment of glucose metabolism may explain partially the Pb2+-induced changes observed in cholinergic function.

Alteration of Glucose Metabolism in the Spinal Cord of Experimental Lead Poisoning Rats. Microdetermination of Glucose Utilization Rate and Distribution Volume.

“…It is thus suggested that utilization as well as uptake of glucose were deteriorated by lead in the anterior horn of the spinal cord. This is in line of observations of the adverse effects of lead on glucose metabolism [1][2][3][4] . The anterior horn cell (spinal motor neuron) bodies have the highest values of GUR and DV in the spinal cord 5) .…”

“…The decrease in conversion of [ ] glucose into lactate, citrate and malate was observed in cerebral cortex slices obtained from two groups of rats with mean blood lead (BPb) concentrations of 31.8 and 54.2 µg/dl, respectively, which had been given drinking water containing 200 or 600 ppm of lead for 20 days 1) . The conversion rate of [ 14 C] glucose to 14 CO 2 was reduced in brain capillaries isolated from cerebral cortex of calves with BPb of 118 ± 0.19 µg/dl, which were given 15 mg/kg bw of lead acetate orally for 7 to 8 days, showing no histopathological changes 2) .…”

Decreased Expression of the Voltage-Dependent Anion Channel in Differentiated PC-12 and SH-SY5Y Cells Following Low-Level Pb Exposure

“…Although there have been many studies devoted to studying the effects of Pb exposure, the molecular mechanisms behind the subtle neurotoxic effects of lower levels of Pb remain largely unknown. However, disrupted energy metabolism is one mechanism that has been proposed as a possible cause of the behavioral abnormalities and brain dysfunction induced by Pb (Sterling et al, 1982).…”