MRI characterization of structural mouse brain changes in response to chronic exposure to the glufosinate ammonium herbicide.
Glufosinate ammonium (GLA) is the active component of herbicides widely used in agriculture, truck farming, or public domains. GLA acts by inhibiting the plant glutamine synthetase (GlnS). It also inhibits mammalian GlnS in vitro and ex vivo. In the central nervous system this enzyme is exclusively localized in glial cells. Whereas acute neurotoxic effects of GLA are well documented, long-term effects during chronic exposure at low doses remain largely undisclosed. In the present work, C57BL/6J mice were treated intraperitoneally with 2.5, 5, and 10 mg/kg of GLA three times a week during 10 weeks. Cerebral magnetic resonance imaging (MRI) experiments were performed at high field (9.4 T) and the images were analyzed with four texture analysis (TA) methods. TA highlighted structural changes in seven brain structures after chronic GLA treatments. Changes are dose dependent and can be seen at a dose as low as 2.5 mg/kg for two areas, namely hippocampus and somatosensorial cortex. Glial fibrillary acidic protein (GFAP) expression in the same seven brain structures and GlnS activity in the hippocampus and cortex areas were also studied. The number of GFAP-positive cells is modified in six out of the seven areas examined. GlnS activity was significantly increased in the hippocampus but not in the cortex. These results indicate some kind of suffering at the cerebral level after chronic GLA treatment. Changes in TA were compared with the modification of the number of GFAP-positive astrocytes in the studied brain areas after GLA treatment. We show that the noninvasive MRI-TA is a sensitive method and we suggest that it would be a very helpful tool that can efficiently contribute to the detection of cerebral alterations in vivo during chronic exposure to xenobiotics.
Meme
Sandra
S
Centre de Biophysique Moléculaire, CNRS UPR4301, Rue Charles Sadron, 45071 Orléans Cedex, France. sandra.meme@cnrs-orleans.fr
Calas
André-Guilhem
AG
Montécot
Céline
C
Richard
Oliver
O
Gautier
Hélène
H
Gefflaut
Thierry
T
Doan
Bich Thuy
BT
Même
William
W
Pichon
Jacques
J
Beloeil
Jean-Claude
JC
D000613:Aminobutyrates / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000613:Aminobutyrates; D005904:Glial Fibrillary Acidic Protein; D006540:Herbicides; C003121:phosphinothricin