Elsevier

NeuroToxicology

Volume 30, Issue 5, September 2009, Pages 772-776
NeuroToxicology

Primary brain targets of nerve agents: The role of the amygdala in comparison to the hippocampus

https://doi.org/10.1016/j.neuro.2009.06.011Get rights and content

Abstract

Exposure to nerve agents and other organophosphorus acetylcholinesterases used in industry and agriculture can cause death, or brain damage, producing long-term cognitive and behavioral deficits. Brain damage is primarily caused by the intense seizure activity induced by these agents. Identifying the brain regions that respond most intensely to nerve agents, in terms of generating and spreading seizure activity, along with knowledge of the physiology and biochemistry of these regions, can facilitate the development of pharmacological treatments that will effectively control seizures even if administered when seizures are well underway. Here, we contrast the pathological (neuronal damage) and pathophysiological (neuronal activity) findings of responses to nerve agents in the amygdala and the hippocampus, the two brain structures that play a central role in the generation and spread of seizures. The evidence so far suggests that exposure to nerve agents causes significantly more damage in the amygdala than in the hippocampus. Furthermore, in in vitro brain slices, the amygdala generates prolonged, seizure-like neuronal discharges in response to the nerve agent soman, at a time when the hippocampus generates only interictal-like activity. In vivo experiments are now required to confirm the primary role that the amygdala seems to play in nerve agent-induced seizure generation.

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Conflict of interest statement

No competing interests.

Acknowledgements

We thank Adriana Souza for assistance in the pathological analysis. This work was supported by the National Institutes of Health CounterACT Program through the National Institute of Neurological Disorders and Stroke (award #U01 NS058162-01), and the Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division grant #1.E0021_07_US_C.

References (70)

  • M. Isokawa-Akesson et al.

    Structurally stable burst and synchronized firing in human amygdala neurons: auto- and cross-correlation analyses in temporal lobe epilepsy

    Epilepsy Res

    (1987)
  • M.J. Joosen et al.

    Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning

    NeuroToxicology

    (2009)
  • E.W. Kairiss et al.

    The development of the interictal spike during kindling in the rat

    Brain Res

    (1984)
  • G. Lallement et al.

    Effects of soman-induced seizures on different extracellular amino acid levels and on glutamate uptake in rat hippocampus

    Brain Res

    (1991)
  • G. Lallement et al.

    Changes in hippocampal acetylcholine and glutamate extracellular levels during soman-induced seizures: influence of septal cholinoceptive cells

    Neurosci Lett

    (1992)
  • G. Lallement et al.

    Medical management of organophosphate-induced seizures

    J Physiol (Paris)

    (1998)
  • J.H. McDonough et al.

    Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology

    Neurosci Biobehav Rev

    (1997)
  • D.C. McIntyre et al.

    Kindling mechanisms: current progress on an experimental epilepsy model

    Prog Neurobiol

    (1986)
  • P. Mohapel et al.

    Differential sensitivity of various temporal lobe structures in the rat to kindling and status epilepticus induction

    Epilepsy Res

    (1996)
  • K. Morimoto et al.

    Kindling and status epilepticus models of epilepsy: rewiring the brain

    Prog Neurobiol

    (2004)
  • T. Myhrer et al.

    Soman-induced convulsions in rats terminated with pharmacological agents after 45 min: neuropathology and cognitive performance

    Neurotoxicology

    (2005)
  • A. Pitkänen et al.

    Amygdala damage in experimental and human temporal lobe epilepsy

    Epilepsy Res

    (1998)
  • W.P. Schecter

    Cholinergic symptoms due to nerve agent attack: a strategy for management

    Anesthesiol Clin North America

    (2004)
  • T.M. Shih et al.

    Organophosphorus nerve agents-induced seizures and efficacy of atropine sulfate as anticonvulsant treatment

    Pharmacol Biochem Behav

    (1999)
  • T. Shih et al.

    Control of nerve agent induced seizures is critical for neuroprotection and survival

    Toxicol Applied Pharm

    (2003)
  • Y. Solberg et al.

    The role of excitotoxicity in organophosphorous nerve agents central poisoning

    TiPS

    (1997)
  • V. Aroniadou-Anderjaska et al.

    Mechanisms regulating GABAergic inhibitory transmission in the basolateral amygdala: implications for epilepsy and anxiety disorders

    Amino Acids

    (2007)
  • M. Avoli

    Do interictal discharges promote or control seizures? Experimental evidence from an in vitro model of epileptiform discharge

    Epilepsia

    (2001)
  • J. Bajgar et al.

    Biochemical and behavioral effects of soman vapors in low concentrations

    Inhal Toxicol

    (2004)
  • J. Bajgar

    Complex view on poisoning with nerve agents and organophosphates

    Acta Medica (Hradec Kralove)

    (2005)
  • M. Barbarosie et al.

    CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures

    J Neurosci

    (1997)
  • W.B. Baze

    Soman-induced morphological changes: an overview in the nonhuman primate

    J Appl Toxicol

    (1993)
  • M.F. Braga et al.

    Bidirectional modulation of GABA release by presynaptic glutamate receptor 5 kainate receptors in the basolateral amygdala

    J Neurosci

    (2003)
  • M.F. Braga et al.

    The physiological role of kainate receptors in the amygdala

    Mol Neurobiol

    (2004)
  • M.A. Brown et al.

    Review of health consequences from high, intermediate, and low-level exposure to organophosphorus nerve agents

    J Appl Toxicol

    (1998)
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