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Delayed reduction of hippocampal synaptic transmission and spines following exposure to repeated subclinical doses of organophosphorus pesticide in adult mice.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2012 Jan; Vol. 125 (1), pp. 196-208. Date of Electronic Publication: 2011 Sep 26. - Publication Year :
- 2012
-
Abstract
- Agricultural and household organophosphorus (OP) pesticides inhibit acetylcholinesterase (AchE), resulting in increased acetylcholine (Ach) in the central nervous system. In adults, acute and prolonged exposure to high doses of AchE inhibitors causes severe, clinically apparent symptoms, followed by lasting memory impairments and cognitive dysfunction. The neurotoxicity of repeated environmental exposure to lower, subclinical doses of OP pesticides in adults is not as well studied. However, repeated exposure to acetylcholinesterase inhibitors, such as chlorpyrifos (CPF), pyridostigmine, and sarin nerve agent, has been epidemiologically linked to delayed onset symptoms in Gulf War Illness and may be relevant to environmental exposure in farm workers among others. We treated adult mice with a subclinical dose (5 mg/kg) of CPF for 5 consecutive days and investigated hippocampal synaptic transmission and spine density early (2-7 days) and late (3 months) after CPF administration. No signs of cholinergic toxicity were observed at any time during or after treatment. At 2-7 days after the last injection, we found increased synaptic transmission in the CA3-CA1 region of the hippocampus of CPF-treated mice compared with controls. In contrast, at 3 months after CPF administration, we observed a 50% reduction in synaptic transmission likely due to a corresponding 50% decrease in CA1 pyramidal neuron synaptic spine density. This study is the first to identify a biphasic progression of synaptic abnormalities following repeated OP exposure and suggests that even in the absence of acute cholinergic toxicity, repeated exposure to CPF causes delayed persistent damage to the adult brain in vivo.
- Subjects :
- Acetylcholinesterase metabolism
Animals
CA1 Region, Hippocampal drug effects
CA1 Region, Hippocampal enzymology
CA1 Region, Hippocampal pathology
CA1 Region, Hippocampal physiopathology
CA3 Region, Hippocampal drug effects
CA3 Region, Hippocampal enzymology
CA3 Region, Hippocampal pathology
CA3 Region, Hippocampal physiopathology
Cell Count
Dendritic Spines pathology
Dose-Response Relationship, Drug
Hippocampus enzymology
Hippocampus pathology
Hippocampus physiopathology
Male
Mice
Mice, Inbred C57BL
Patch-Clamp Techniques
Pyramidal Cells pathology
Time Factors
Chlorpyrifos toxicity
Dendritic Spines drug effects
Hippocampus drug effects
Pesticides toxicity
Pyramidal Cells drug effects
Synaptic Transmission drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0929
- Volume :
- 125
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 21948870
- Full Text :
- https://doi.org/10.1093/toxsci/kfr253