An In Vivo and In Silico Experimental Approach on Rats' Neurobehaviour upon Treatment with Atrazine and Manganese

In this study, adult Wistar rats treated with atrazine (ATZ) and manganese (Mn) for 28 days were used to examine the impact of ATZ-Mn co-exposure on neurobehavioral, neurochemical, and histological effects in vivo and KEGG pathway analysis in silico. Forty rats (n = 40; 150 ± 10 g) were arbitrarily assigned into five (5) groups: control (2 mL/kg of corn oil; n = 8), ATZ-only (ATZ 10 mg/kg; n = 8), Mn-only and two ATZ + Mn groups at different doses of manganese: low dose and high dose (Mn₁; 2.5, Mn₂;10 mg/kg: n = 8/rat) respectively. The ATZ-only rat cohort resulted in hypoactivity, reduced antioxidant systems, increased oxido-inflammatory stress and caused severe neuronal damage in the cerebrum and cerebellum. Conversely, ATZ + Mn co-treatment showed dose-dependent reversal of behavioral abnormalities, protection against ATZ-induced oxidative stress and inflammation, and restoration of cerebral and cerebellar neuronal damage. Protein-protein interaction network analysis identified 20 hub genes from 206 target genes relevant to Mn-mediated neuroprotection. Gene ontology revealed hub gene associations with cytoplasmic localization, cell communication, immune response, apoptosis regulation, transcription factor activity, and catalytic activity. KEGG pathway analysis showed enrichment in prolactin and p53 signaling pathways. In conclusion, co-exposure to Mn at a hormetic dose elicited an increased neurobehavioral response, modulating antioxidant status, anti-inflammation, reducing the apoptotic process, and alterations in gene and protein networks may drive Mn-induced neuroprotection against ATZ-induced neurotoxicity. This study highlights the potential protective role of low-dose Mn supplementation against ATZ-induced neurotoxicity and provides insights into the underlying mechanisms.