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Primary hippocampal neuronal cell death induction after acute and repeated paraquat exposures mediated by AChE variants alteration and cholinergic and glutamatergic transmission disruption.
- Source :
-
Toxicology [Toxicology] 2017 Sep 01; Vol. 390, pp. 88-99. Date of Electronic Publication: 2017 Sep 12. - Publication Year :
- 2017
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Abstract
- Paraquat (PQ) is a widely used non-selective contact herbicide shown to produce memory and learning deficits after acute and repeated exposure similar to those induced in Alzheimer's disease (AD). However, the complete mechanisms through which it induces these effects are unknown. On the other hand, cholinergic and glutamatergic systems, mainly in the hippocampus, are involved on learning, memory and cell viability regulation. An alteration of hippocampal cholinergic or glutamatergic transmissions or neuronal cell loss may induce these effects. In this regard, it has been suggested that PQ may induce cell death and affect cholinergic and glutamatergic transmission, which alteration could produce neuronal loss. According to these data, we hypothesized that PQ could induce hippocampal neuronal loss through cholinergic and glutamatergic transmissions alteration. To prove this hypothesis, we evaluated in hippocampal primary cell culture, the PQ toxic effects after 24h and 14 consecutive days exposure on neuronal viability and the cholinergic and glutamatergic mechanisms related to it. This study shows that PQ impaired acetylcholine levels and induced AChE inhibition and increased CHT expression only after 14days exposure, which suggests that acetylcholine levels alteration could be mediated by these actions. PQ also disrupted glutamate levels through induction of glutaminase activity. In addition, PQ induced, after 24h and 14days exposure, cell death on hippocampal neurons that was partially mediated by AChE variants alteration and cholinergic and gultamatergic transmissions disruption. Our present results provide new view of the mechanisms contributing to PQ neurotoxicity and may explain cognitive dysfunctions observed after PQ exposure.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Acetylcholinesterase genetics
Animals
Behavior, Animal drug effects
Cell Death drug effects
Cell Survival drug effects
Cells, Cultured
Choline O-Acetyltransferase genetics
Choline O-Acetyltransferase metabolism
Cognition drug effects
Dose-Response Relationship, Drug
GPI-Linked Proteins genetics
GPI-Linked Proteins metabolism
Gestational Age
Glutaminase genetics
Glutaminase metabolism
Hippocampus enzymology
Hippocampus pathology
Hippocampus physiopathology
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Neurons enzymology
Neurons pathology
Primary Cell Culture
RNA Interference
Rats, Wistar
Time Factors
Transfection
Acetylcholine metabolism
Acetylcholinesterase metabolism
Glutamic Acid metabolism
Herbicides toxicity
Hippocampus drug effects
Neurons drug effects
Paraquat toxicity
Synaptic Transmission drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 390
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 28916328
- Full Text :
- https://doi.org/10.1016/j.tox.2017.09.008