Ferrous sulfate and lipopolysaccharide co-exposure induce neuroinflammation, neurobehavioral motor deficits, neurodegenerative and histopathological biomarkers relevant to Parkinson's disease-like symptoms in Wistar rats.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra region of the brain. Although iron is one of the essential micronutrients in the brain, its excess exposure and accumulation in the brain substantia nigra and striatum regions may induce critical pathological changes relevant to PD. This study has evaluated neurobehavioral, biochemical, and structural alterations resembling PD-like symptoms induced through a 4-week co-exposure of ferrous sulfate (FeSO₄) with lipopolysaccharide (LPS) in Wistar rats. Our results revealed motor deficits, oxidative stress, neuroinflammation, iron dysregulation, protein aggregation, ferroptosis, and apoptotic cell death. Notably, we observed decreased tyrosine hydroxylase levels and increased α-synuclein accumulation, consistent with PD pathology. The immunohistopathological assessments showed astrocyte activation and iron deposition, supporting their roles in neuroinflammation and oxidative stress. Furthermore, we identified alterations in apoptosis and ferroptosis markers, suggesting dose-related involvement of FeSO₄ in neuronal death in the rat brain. These findings have highlighted the multifaceted mechanisms during the co-exposure of FeSO₄ and LPS-induced neurodegeneration and neuroinflammation relevant to PD. This study emphasizes that therapeutic targeting of these pathological mechanisms may offer a promising therapeutic intervention in PD.