Altered energy status of primary cerebellar granule neuronal cultures from rats exposed to lead in the pre- and neonatal period.
This paper examines the effect of pre- and neonatal exposure of rats to lead (0.1% lead acetate in drinking water, resulting in rat offspring whole blood lead concentration (Pb-B) 4μg/dL) on the energy status of neuronal mitochondria by measuring changes in ATP, ADP, AMP, adenosine, TAN concentration, adenylate energy charge value (AEC) and mitochondrial membrane potential in primary cerebellar granule neurons (CGC) in dissociated cultures. Fluorescence studies were performed to imaging and evaluate mitochondria mass, mitochondrial membrane potential, intracellular and mitochondrial reactive oxygen species (ROS) production. The Na(+)/K(+) ATPase activity in intact CGC was measured spectrophotometrically. Our data shows that pre- and neonatal exposure of rats to Pb, even below the threshold of whole blood Pb value considered safe for people, affects the energy status of cultured primary cerebellar granule neurons through a decrease in ATP and TAN concentrations and AEC value, inhibition of Na(+)/K(+) ATPase, and increase in intracellular and mitochondrial ROS concentration. These observations suggest that even these low levels of Pb are likely to induce important alterations in neuronal function that could play a role in neurodegeneration.
Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Żołnierska 48, Szczecin, Poland. ika@sci.pam.szczecin
I
I
Baranowska-Bosiacka
I
I
Gutowska
C
C
Marchetti
M
M
Rutkowska
M
M
Marchlewicz
A
A
Kolasa
A
A
Prokopowicz
I
I
Wiernicki
K
K
Piotrowska
M
M
Baśkiewicz
K
K
Safranow
B
B
Wiszniewska
D
D
Chlubek
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D017382:Reactive Oxygen Species; D007854:Lead; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase