chlorpyrifos toxicity in mouse cultured cerebellar granule neurons at different stages of development: additive effect on glutamate-induced excitotoxicity
نویسندگان
چکیده
objective: chlorpyrifos (cpf) is a neurotoxic organophosphorus (op) insecticide. its mechanism of action includes oxidative stress, excitotoxicity, and inhibition of the acetylcholinesterase enzyme (ache). the aim of the present study is to investigate cpf toxicity in mature and immature cerebellar granule neurons (cgns), as well as its effect on glutamate induced excitotoxicity. materials and methods: this study was an in vitro experimental study performed on mice cultured cgns. immature and mature neurons were exposed to different concentrations of cpf (1-1000 μm) and glutamate (10-600 μm) for 48 hours after which we used the mtt assay to measure cytotoxicity. immature neurons had exposure to cpf for 5 days in order to evaluate the cytotoxic effect on developing neurons. mature neurons received sub-lethal concentrations of cpf (10, 100 μm) combined with different concentrations of glutamate. ache activity and reactive oxygen species (ros) generation were assessed after treatments. results: immature cgns had increased sensitivity to cpf toxicity compared to mature neurons. we observed significantly greater ros production in immature compared to mature neurons, however ache activity was more inhibited in mature neurons. although cpf toxicity was not well correlated with ache inhibition, it correlated well with ros production. glutamate toxicity was potentiated by sub-lethal concentration of cpf, however glutamate induced ros production was not affected. the results suggested that cpf potentiated glutamate toxicity by mechanisms other than oxidative stress. conclusion: cpf toxicity differed in mature and immature neurons. potentiated glutamate toxicity by cpf implied that cpf exposure might be a risk factor for neurodegenerative disease.
منابع مشابه
Chlorpyrifos Toxicity in Mouse Cultured Cerebellar Granule Neurons at Different Stages of Development: Additive Effect on Glutamate-Induced Excitotoxicity
OBJECTIVE Chlorpyrifos (CPF) is a neurotoxic organophosphorus (OP) insecticide. Its mechanism of action includes oxidative stress, excitotoxicity, and inhibition of the acetylcholinesterase enzyme (AChE). The aim of the present study is to investigate CPF toxicity in mature and immature cerebellar granule neurons (CGNs), as well as its effect on glutamate induced excitotoxicity. MATERIALS AND...
متن کاملMitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells.
Mitochondria within cultured rat cerebellar granule cells have a complex influence on cytoplasmic free Ca2+ ([Ca2+]c) responses to glutamate. A decreased initial [Ca2+]c elevation in cells whose mitochondria are depolarized by inhibition of the ATP synthase and respiratory chain (conditions which avoid ATP depletion) was attributed to enhanced Ca2+ extrusion from the cell rather than inhibited ...
متن کاملMitochondrial membrane potential and glutamate excitotoxicity in cultured cerebellar granule cells.
The relationship between changes in mitochondrial membrane potential (Deltapsi(m)) and the failure of cytoplasmic Ca(2+) homeostasis, delayed Ca(2+)deregulation (DCD), is investigated for cultured rat cerebellar granule cells exposed to glutamate. To interpret the single-cell fluorescence response of cells loaded with tetramethylrhodamine methyl ester (TMRM(+)) or rhodamine-123, we devised and ...
متن کاملScreening seven Iranian medicinal plants for protective effects against β-Amyloid-induced cytotoxicity in cultured cerebellar granule neurons
Background and objectives: Alzheimer's disease (AD) as a neurodegenerative disorder is the most common form of dementia in the elderly. According to the amyloid hypothesis, accumulation of amyloid beta (Aβ) plaques, which are mostly constituted of Aβ peptide aggregates, triggers pathological cascades that lead to neuronal cell death. Thus, modulation of Aβ toxicity is the hopef...
متن کاملNeuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study
Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss(Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pupsCerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were preparedand cultured. The experiments were performed after 8 days in culture. The plant was collected fromthe northeastern part (Ruin re...
متن کاملNeuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study
Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss(Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pupsCerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were preparedand cultured. The experiments were performed after 8 days in culture. The plant was collected fromthe northeastern part (Ruin re...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
cell journalجلد ۱۸، شماره ۳، صفحات ۴۶۴-۴۷۲
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023