Maturation-dependent neurotoxicity of lead acetate in vitro: implication of glial reactions.
Despite a wealth of data on the neurotoxic effects of lead at the cellular and molecular levels, the reasons for its development-dependent neurotoxicity are still unclear. Here, the maturation-dependent effects of lead acetate were analyzed in immature and differentiated brain cells cultured in aggregates. Markers of general cytotoxicity as well as cell-type-specific markers of glial and neuronal cells showed that immature brain cells were more sensitive to lead than the differentiated counterparts, demonstrating that the development-dependent neurotoxicity of lead can be reproduced in aggregating brain cell cultures. After 10 days of treatment, astrocytes were found to be more affected by lead acetate than neurons in immature cultures, and microglial cells were strongly activated. Eleven days after cessation of the treatment, lead acetate caused a partial loss of astrocytes and an intense reactivity of the remaining ones. Furthermore, microglial cells expressed a macrophagic phenotype, and the loss of activity of neuron-specific enzymes was aggravated. In differentiated cultures, no reactive gliosis was found. It is hypothetized that the intense glial reactions (microgliosis and astrogliosis) observed in immature cultures contribute to the development-dependent neurotoxicity of lead.
Zurich
Marie-Gabrielle
MG
Institute of Physiology, University of Lausanne, Lausanne, Switzerland.
Eskes
Chantra
C
Honegger
Paul
P
Bérode
Michèle
M
Monnet-Tschudi
Florianne
F
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002247:Carbon Isotopes; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005970:Glutamate Synthase / Q000378:metabolism; D007150:Immunohistochemistry; D037102:Lectins / Q000737:chemistry; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D013687:Telencephalon; D013936:Thymidine / Q000378:metabolism
D002247:Carbon Isotopes; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D009942:Organometallic Compounds; D005970:Glutamate Synthase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C008261:lead acetate; D013936:Thymidine