The influence of low-level sarin inhalation exposure on spatial memory in rats

Kassa, Jiřı́; Koupilová, M; Vachek, Josef

doi:10.1016/s0091-3057(01)00592-5

Cited by 42 publications

(22 citation statements)

References 15 publications

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“…Effects of low-dose soman on an equilibrium test in rhesus monkeys were reported to wear off 24 h after exposure (Switzer et al, 1990). Exposure to low-dose sarin has been recently reported to induce a decrease in activity and mobility, alteration of gait, and increase in stereotyped behavior and excitability in rats that persisted 3 to 12 months (Kassa et al, 2001a), as well as a deficit in Y-maze performance that subsided 3 weeks after exposure (Kassa et al, 2001b).…”

Section: Discussionmentioning

confidence: 99%

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Scremin¹,

Shih²,

Huynh³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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We tested the hypothesis that pyridostigmine bromide (PB) intake and/or low-level sarin exposure, suggested by some as causes of the symptoms experienced by Persian Gulf War veterans, induce neurobehavioral dysfunction that outlasts their effects on cholinesterase. Adult male Sprague-Dawley rats were treated during 3 weeks with s.c. saline, PB in drinking water (80 mg/l), sarin (62.5 g/kg; 0.5ϫ LD 50 , three times/week s.c.), or PB in drinking water ϩ sarin. Animals were tested for passive avoidance, nociceptive threshold, acoustic startle, and open field activity 2, 4, or 16 weeks after treatment. Two weeks after sarin, acoustic startle was enhanced, whereas distance explored in the open field decreased. These effects were absent with PB ϩ sarin or PB by itself. No effect on any variable was found at 4 weeks, whereas at 16 weeks sarin induced a decrease and PB ϩ sarin induced an increase in habituation in the open field test. Nociceptive threshold was elevated in the PB ϩ sarin group at 16 weeks. No effect of treatment on passive avoidance was noted in any group. Brain regional acetylcholinesterase and cholineacetyltransferase activities were not affected at any time after treatment, but muscarinic receptors were down-regulated in hippocampus, caudate putamen, and mesencephalon in the sarin group at 2 weeks. In conclusion, this study gives further support to the use of PB against nerve agent poisoning and does not support the hypothesis that delayed symptoms experienced by Persian Gulf War veterans could be due to PB, alone or in association with low-level sarin exposure.

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Section: Discussionmentioning

confidence: 99%

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Scremin¹,

Shih²,

Huynh³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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“…2,7) In experimental studies, cognitive deficit was found to last days to months after cessation of OP pesticides exposure. 8,9) The long-lasting neuropsychiatric changes suggest that the central nervous system has been permanently damaged.COPIND is sometimes delayed in occurrence, independent of acute toxicity.10) It was found among sheep dippers that long term (2 months later) neurotoxic effects occurred independent of symptoms arising from acute OP pesticides exposure. Only a slight increase in immediate effects but a significant increase in long-term effects were detected compared to the controls 11)…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Chlorpyrifos Induces Delayed Cytotoxicity after Withdrawal in Primary Hippocampal Neurons through Extracellular Signal-Regulated Kinase Inhibition

Peng

et al. 2009

Biological & Pharmaceutical Bulletin

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Organophosphorus (OP) pesticides are extensively used for control of insects around the home and in agricultural practice. However, they can pose a threat to public health. OP pesticides are known to cause millions of acute poisoning cases per year around the world.1) Besides acute poisoning, OP pesticide exposure causes chronic neurological consequences, especially those related to poor neuropsychiatric changes or neurobehavioral performances in some cognitive domains or mood domain.2) The chronic neurological consequence is called chronic OP-induced neuropsychiatric disorder (COPIND) or organophosphorus ester-induced chronic neurotoxicity (OPICN), [3][4][5] which can occur not only after acute OP pesticide intoxication but after long-term low-level exposure.The mechanism of acute toxicity of OP pesticide has been fully studied and understood. The symptom after absorption of OP pesticide is acute cholinergic syndrome due to inhibition of acetylcholinersterase (AChE) that degrades acetylcholine (ACh).6) By contrast, the mechanism of chronic neurological consequence or COPIND is not very clear now.COPIND is usually long-lasting. Agricultural workers performed worse on tests of cognitive and psychomotor function in 2 years after OP pesticide intoxication. 2,7) In experimental studies, cognitive deficit was found to last days to months after cessation of OP pesticides exposure. 8,9) The long-lasting neuropsychiatric changes suggest that the central nervous system has been permanently damaged.COPIND is sometimes delayed in occurrence, independent of acute toxicity.10) It was found among sheep dippers that long term (2 months later) neurotoxic effects occurred independent of symptoms arising from acute OP pesticides exposure. Only a slight increase in immediate effects but a significant increase in long-term effects were detected compared to the controls 11); Women greenhouse workers were found to show no abnormal neurological changes during the working season despite their contact with OP pesticides. However, abnormal neurological changes occurred after the working season.12) Song et al. 13) found that neurotoxicity appeared after several days' delay upon termination of OP pesticide exposure to rats; Prendergast et al. 14) found the impairment of working memory after OP pesticide withdrawal. These findings suggest that COPIND may not derive from the direct effect of OP pesticide to some extent. The mechanism of delayed neurotoxicity remains little known.In vitro studies may help elucidate the mechanism of OP pesticide neurotoxicity. In this study, the delayed cytotoxicity of chlorpyrifos (CPF) was probed in cultured rat hippocampal neurons. CPF was chosen since it has been a widely used OP pesticide and confirmed to induce long-term neurotoxicity in vivo 8,15,16) and neurotoxicity in vitro. 17,18) Primary hippocampal neurons were used, for hippocampus was the cognition-related brain region and vulnerable to CPF insult. 16,19,20) In the present study, no detectable cytotoxicity was found in the cultured hippocamp...

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“…The reactivating efficacy of oximes studied is investigated by the calculation of percentage of reactivation of NA-inhibited AChE in peripheral (mostly blood and diaphragm) and central (central nervous system) compartment in rats using modified Ellman method for the measurement of AChE activity. Finally, the potency of chosen oximes to eliminate NA-induced signs of neurotoxicity (neuroprotective efficacy) was evaluated using Functional observatory battery (FAB) consisting of more than 40 parameters of sensoric, motoric and autonomic nervous functions in rats [17][18][19][20][21][22][23] . Till today, two new AChE reactivators -K027 (1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium )propane dibromide) and K048 (1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide) were developed 9,10 .…”

Section: In Vivo Testingmentioning

confidence: 99%

Strategy for the development of new acetylcholinesterase reactivators - antidotes used for treatment of nerve agent poisonings

Kuča¹,

Cabal²,

Jun³

et al. 2005

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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The influence of low-level sarin inhalation exposure on spatial memory in rats

Cited by 42 publications

References 15 publications

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Delayed Neurologic and Behavioral Effects of Subtoxic Doses of Cholinesterase Inhibitors

Chlorpyrifos Induces Delayed Cytotoxicity after Withdrawal in Primary Hippocampal Neurons through Extracellular Signal-Regulated Kinase Inhibition

Strategy for the development of new acetylcholinesterase reactivators - antidotes used for treatment of nerve agent poisonings

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