Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure

Abstract

Systemic inflammation triggered by lipopolysaccharide (LPS) administration disrupts blood-brain barrier (BBB) homeostasis in animal models. This event leads to increased susceptibility of several encephalic structures to potential neurotoxicants present in the bloodstream. In this study, we investigated the effects of alternate intraperitoneal injections of LPS on BBB permeability, social recognition memory and biochemical parameters in the striatum 24 h and 60 days after treatments. In addition, we investigated whether the exposure to a moderate neurotoxic dose of the herbicide paraquat could potentiate LPS-induced neurotoxicity. LPS administration caused a transient disruption of BBB integrity, evidenced by increased levels of exogenously administered sodium fluorescein in the striatum. Also, LPS exposure caused delayed impairment in social recognition memory (evaluated at day 38 after treatments) and increase in the striatal levels of 3-nitrotyrosine. These events were observed in the absence of significant changes in motor coordination and in the levels of tyrosine hydroxylase (TH) in the striatum and substantia nigra. PQ exposure, which caused a long-lasting decrease of striatal mitochondrial complex I activity, did not modify LPS-induced behavioral and striatal biochemical changes. The results indicate that systemic administration of LPS causes delayed social recognition memory deficit and striatal nitrosative stress in adult mice and that the coexposure to a moderately toxic dose of PQ did not magnify these events. In addition, PQ-induced inhibition of striatal mitochondrial complex I was also not magnified by LPS exposure, indicating the absence of synergic neurotoxic effects of LPS and PQ in this experimental model.

The influence of preconditioning with low dose of LPS on paraquat-induced neurotoxicity, microglia activation and expression of α-synuclein and synphilin-1 in the dopaminergic system

“…This study was planned to check if minor inflammatory processes and oxidative insults, that often pass unattended with medical help, could contribute to the slowly progressing neurodegenerative processes, similar to PD. Therefore, the doses of LPS (10 μg/kg) used here were small, as compared to the previous studies (1–7 mg/kg, own data not shown and [ 30 ]), and did not induce any sickness behavior.…”

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…Gonçalves et al (2018) administered 5 mg/kg of paraquat intraperitoneally on the 2nd, 4th, 6th, and 7th day in Swiss male mice. Their data for open-field, rotarod, neurological severity score, and social recognition tests revealed that the systemic administration of lipopolysaccharide (3, 5, and 7 mg/kg, intraperitoneally) induced slower social recognition behavioral deficit and striatal stress in adult mice [ 183 ]. Chinta et al (2018) administered a cumulative of 42 mg/kg of paraquat intraperitoneally (7 mg/kg at two-day intervals for a total of six doses) in C57Bl6/J (p16-3MR) mice models.…”

Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cells-mediated protection for Paraquat-induced acute lung injury

“…Multiple organs such as liver, kidney, heart and central nervous system can be affected; but lung is the primary target of PQ [ 14 , 20 ]. PQ is actively taken up in a concentration dependent manner and accumulates at particularly high levels in Clara cells and epithelial cells [ 5 , 10 , 13 , 18 ]. PQ poisoning initially leads to acute lung injury (ALI), and ultimately to lung fibrosis or subsequent respiratory failure, which is the most common cause of death from PQ [ 12 ].…”