Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice
NeuroToxicology. 2008-07-01; 29(4): 740-747
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1. Neurotoxicology. 2008 Jul;29(4):740-7. doi: 10.1016/j.neuro.2008.04.020. Epub
2008 May 4.
Chronic exposure to glufosinate-ammonium induces spatial memory impairments,
hippocampal MRI modifications and glutamine synthetase activation in mice.
Calas AG(1), Richard O, Même S, Beloeil JC, Doan BT, Gefflaut T, Même W, Crusio
WE, Pichon J, Montécot C.
(1)Laboratoire de Neurobiologie, UPRES EA 2633, Université d’Orléans, Orléans,
Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide,
acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal
accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it
allows neurotransmitter glutamate recycling within astroglia. Clinical studies
report that an acute GLA ingestion induces convulsions and memory impairment in
humans. Toxicological studies performed at doses used for herbicidal activity
showed that GLA is probably harmless at short or medium range periods. However,
effects of low doses of GLA on chronically exposed subjects are not known. In our
study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5
and 10mg/kg of GLA. Effects of this chronic treatment were assessed at
behavioral, structural and metabolic levels by using tests of spatial memory,
locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI)
texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA
treatments have effects neither on anxiety nor on locomotor activity of mice but
at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of
hippocampal texture and (3) a significant increase in hippocampal GS activity. It
is suggested that these modifications may be causally linked one to another.
Since glutamate is the main neurotransmitter in hippocampus where it plays a
crucial role in spatial memory, hippocampal MRI texture and spatial memory
alterations might be the consequences of hippocampal glutamate homeostasis
modification revealed by increased GS activity in hippocampus. The present study
provides the first data that show cerebral alterations after chronic exposure to
PMID: 18562008 [Indexed for MEDLINE]