PMID- 29611151 OWN - NLM STAT- MEDLINE DCOM- 20181106 LR - 20191210 IS - 1476-3524 (Electronic) IS - 1029-8428 (Linking) VI - 34 IP - 3 DP - 2018 Oct TI - Perinatal Glyphosate-Based Herbicide Exposure in Rats Alters Brain Antioxidant Status, Glutamate and Acetylcholine Metabolism and Affects Recognition Memory. PG - 363-374 LID - 10.1007/s12640-018-9894-2 [doi] AB - Glyphosate-based herbicides (Gly-BHs) lead the world pesticide market. Although are frequently promoted as safe and of low toxicity, several investigations question its innocuousness. Previously, we described that oral exposure of rats to a Gly-BH during pregnancy and lactation decreased locomotor activity and anxiety in the offspring. The aim of the present study was to evaluate the mechanisms of neurotoxicity of this herbicide. Pregnant Wistar rats were supplied orally with 0.2 and 0.4% of Gly-BH (corresponding to 0.65 and 1.30 g/l of pure Gly, respectively) from gestational day (GD) 0, until weaning (postnatal day, PND, 21). Oxidative stress markers were determined in whole brain homogenates of PND90 offspring. The activity of acetylcholinesterase (AChE), transaminases, and alkaline phosphatase (AP) were assessed in prefrontal cortex (PFC), striatum, and hippocampus. Recognition memory was evaluated by the novel object recognition test. Brain antioxidant status was altered in Gly-BH-exposed rats. Moreover, AChE and transaminases activities were decreased and AP activity was increased in PFC, striatum and hippocampus by Gly-BH treatment. In addition, the recognition memory after 24 h was impaired in adult offspring perinatally exposed to Gly-BH. The present study reveals that exposure to a Gly-BH during early stages of rat development affects brain oxidative stress markers as well as the activity of enzymes involved in the glutamatergic and cholinergic systems. These alterations could contribute to the neurobehavioral variations reported previously by us, and to the impairment in recognition memory described in the present work. FAU - Gallegos, Cristina Eugenia AU - Gallegos CE AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. gallegos@criba.edu.ar. FAU - Baier, Carlos Javier AU - Baier CJ AD - Instituto de Investigaciones Bioquimicas de Bahia Blanca (INIBIBB), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, Bahia Blanca, Argentina. FAU - Bartos, Mariana AU - Bartos M AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. FAU - Bras, Cristina AU - Bras C AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. FAU - Dominguez, Sergio AU - Dominguez S AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. FAU - Monaco, Nina AU - Monaco N AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. FAU - Gumilar, Fernanda AU - Gumilar F AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. FAU - Gimenez, Maria Sofia AU - Gimenez MS AD - Departamento de Bioquimica y Ciencias Biologicas, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, IMIBIO-SL, CONICET, San Luis, Argentina. FAU - Minetti, Alejandra AU - Minetti A AD - Laboratorio de Toxicologia, Instituto de Ciencias Biologicas y Biomedicas del Sur (INBIOSUR), Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur (UNS)-CONICET, San Juan 670, 8000, Bahia Blanca, Buenos Aires, Argentina. LA - eng GR - 24/B224/Grant from Secretaria General de Ciencia y Tecnologia of Universidad Nacional del Sur/ PT - Journal Article DEP - 20180402 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Antioxidants) RN - 0 (Herbicides) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 3KX376GY7L (Glutamic Acid) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/*metabolism MH - Acetylcholinesterase/metabolism MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Antioxidants/*metabolism MH - Brain/*drug effects/metabolism MH - Female MH - Glutamic Acid/*metabolism MH - Glutathione Peroxidase/metabolism MH - Herbicides/*toxicity MH - Male MH - Malondialdehyde/metabolism MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*physiopathology MH - Rats MH - Rats, Wistar MH - Recognition, Psychology/*drug effects MH - Thiobarbituric Acid Reactive Substances/metabolism OTO - NOTNLM OT - AChE OT - Glyphosate-containing herbicides OT - Oxidative stress OT - Pregnancy and lactation OT - Recognition memory OT - Transaminases EDAT- 2018/04/04 06:00 MHDA- 2018/11/07 06:00 CRDT- 2018/04/04 06:00 PHST- 2018/01/25 00:00 [received] PHST- 2018/03/21 00:00 [accepted] PHST- 2018/03/08 00:00 [revised] PHST- 2018/04/04 06:00 [pubmed] PHST- 2018/11/07 06:00 [medline] PHST- 2018/04/04 06:00 [entrez] AID - 10.1007/s12640-018-9894-2 [pii] AID - 10.1007/s12640-018-9894-2 [doi] PST - ppublish SO - Neurotox Res. 2018 Oct;34(3):363-374. doi: 10.1007/s12640-018-9894-2. Epub 2018 Apr 2.