title: Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures.
abstract: Xenobiotic exposure is a risk factor in the etiology of neurodegenerative disease. It was recently hypothesized that restricted exposure during brain development could predispose for a neurodegenerative disease later in life. As neuroinflammation contributes to progressive neurodegeneration, it is suspected that neurodevelopmental xenobiotic exposure could elicit a neuroinflammatory process, which over time may assume a detrimental character. We investigated the neurotoxic effects of paraquat (PQ) in three-dimensional whole rat brain cell cultures, exposed during an early differentiation stage, comparing immediate effects-directly post exposure-with long-term effects, 20 days after interrupted PQ-administration. Adverse effects and neuroinflammatory responses were assessed by measuring changes in gene- and protein-expression as well as by determining cell morphology changes. Differentiating neural cultures were highly susceptible to PQ and showed neuronal damage and strong astrogliosis. After the 20-day washout period, neurons partially recovered, whereas astrogliosis persisted, and was accompanied by microglial activation of a neurodegenerative phenotype. Our data shows that immediate and long-term effects of subchronic PQ-exposure differ. Also, PQ-exposure during this window of extensive neuronal differentiation led to a delayed microglial activation, of a character that could promote further pro-inflammatory signals that enable prolonged inflammation, thereby fueling further neurodegeneration.
authors: Swiss Centre for Applied Human Toxicology (SCAHT) , Switzerland; Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland. Electronic address: jenny.sandstrom@unil.ch.
authors: Jenny
authors: J
authors: Sandström von Tobel
authors: Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Debora
authors: D
authors: Zoia
authors: Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Jorane
authors: J
authors: Althaus
authors: Swiss Centre for Applied Human Toxicology (SCAHT) , Switzerland; Department of Human Protein Sciences, University of Geneva, CH-1200 Geneva, Switzerland.
authors: Paola
authors: P
authors: Antinori
authors: Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Julien
authors: J
authors: Mermoud
authors: Department of Human Protein Sciences, University of Geneva, CH-1200 Geneva, Switzerland.
authors: Hui Song
authors: HS
authors: Pak
authors: Swiss Centre for Applied Human Toxicology (SCAHT) , Switzerland; Department of Human Protein Sciences, University of Geneva, CH-1200 Geneva, Switzerland.
authors: Alexander
authors: A
authors: Scherl
authors: Swiss Centre for Applied Human Toxicology (SCAHT) , Switzerland; Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Florianne
authors: F
authors: Monnet-Tschudi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D006540:Herbicides; D010269:Paraquat
keywords: Astrogliosis; M1/M2 phenotype; Microglial activation; Neuroinflammation; Paraquat dichloride