Flaxseed Oil Attenuates Trimethyltin-induced Neurodegeneration via Down-regulation of Inflammatory Activity of Astrocytes

Abstract Trimethyltin chloride (TMT) is an organotin neurotoxicant that selectively targets the hippocampus, and induces selective and progressive neuronal loss, gliosis, neuroinflammation and cognitive deficits, thus resembling critical features of Alzheimer’s diseases (AD). Flaxseed oil (FSO) is anti-inflammatory agent with potent neuroprotective properties. Therefore, the presented study was designed to evaluate the protective effects of flaxseed oil (FSO) continuous pretreatment to alleviate TMT- (8 mg/kg) induced neurodegeneration. Ovariectomized (OVX) female rats were pretreated with FSO (1 ml/kg, orally) for two weeks. At day 14, part of animals received single dose of TMT (8 mg/kg, i.p.) and application of FSO continued for seven more days. Data have convincingly shown that FSO counteracted TMT effects. Specifically, daily administration of FSO improved TMT- induced behavioral manifestations manifested as hyper-excitability, and hyper-responsiveness, reduced neuronal loss, ameliorated expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-6), alleviated astrogliosis and A1-like astrocytes conversion which was related to down-regulation of aromatase/estrogen receptor α signaling, and microgliosis. Together, these findings support beneficial neuroprotective properties of FSO against TMT-induced neurotoxicity and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction.