Short-chain chlorinated paraffins induce hippocampal damage and glycerophospholipids disruption contributing to neurobehavioral deficits in mice

Short-chain chlorinated paraffins (SCCPs), a class of widely used industrial chemicals, have raised significant health concerns due to their persistence, bioaccumulation, and potential neurotoxicity. This study investigated the neurotoxic effects of SCCPs on the hippocampus and their impact on brain glycerophospholipid metabolism in mice. Behavioral tests revealed that 50 mg/kg SCCPs exposure significantly reduced spontaneous activity and impaired learning and memory. Pathological examination showed neuronal damage, including nuclear pyknosis and cytoplasmic vacuolization, in the hippocampus. Biochemical analyses indicated elevated oxidative stress markers (reactive oxygen species, malondialdehyde) and decreased antioxidant levels (glutathione, superoxide dismutase), alongside reduced levels of neurotransmitters (5-Hydroxytryptamine, dopamine, brain-derived neurotrophic factor). Lipidomics analysis identified significant alterations in glycerophospholipid metabolites, such as decreased levels of phosphatidylcholine and phosphatidylserine. Immunohistochemistry demonstrated downregulation of tight junction proteins (Claudin-1, ZO-1), suggesting blood-brain barrier disruption. These findings highlight SCCPs’ potential to induce hippocampal oxidative stress, neurotransmitter dysregulation, decreased claudin-1 expression and glycerophospholipid metabolism disruption, contributing to neurobehavioral deficits. This study provides insights into the mechanisms of SCCPs-induced neurotoxicity and emphasizes their potential implications for brain health.