Polyhexamethylene guanidine phosphate exposure induces abnormal behaviors by disrupting synaptic formation and activity in the cerebral cortex.

backgroundPolyhexamethylene guanidine phosphate (PHMG-p), a commonly utilized ingredient in humidifier disinfectants, has emerged as a primary factor contributing to pulmonary damage, asthmatic conditions, and prenatal complications in South Korea. Nevertheless, the extended neurological impacts resulting from PHMG-p exposure have not been adequately investigated. Our objective was to examine the fundamental mechanisms underlying PHMG-p-triggered neurological dysfunction in a murine model after biocide exposure.

methodsAdult mice aged eight weeks underwent intratracheal instillation (ITI) with either PHMG-p solution (0.9 mg/kg) or saline solution (serving as controls). After a four-week recuperation interval, we examined histopathological features including inflammatory responses and fibrotic alterations in lung tissue. Behavioral performance was assessed through open field testing, Y-maze evaluation, and Rotarod performance tests. Brain tissue molecular characteristics were investigated via RNA sequencing, RT-PCR analysis, and western blot techniques. Cellular composition in neural tissues was determined using immunofluorescence methods.

resultsFour weeks after the exposure, the brains of the mice displayed abnormal neuronal and astrocyte populations owing to activated neuronal death. Notably, exposure to PHMG-p impaired synaptic formation and altered behavioral patterns in the mice. The observed changes appeared to be associated with transfer RNA (tRNA)-mediated neuronal death and synaptic formation, as RNA sequencing-based gene ontology analysis revealed the downregulation of tRNA expression following PHMG-p exposure.

conclusionThese findings enhance our understanding of the pathophysiological mechanisms triggered by PHMG-p exposure.