Dopaminergic agonist pramipexole improves memory and increases IL-۱۰ production in LPS-challenged rats

Objective(s): A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF)  levels in lipopolysaccharide (LPS) challenged-rats. Materials and Methods: Male Wistar rats were divided into ۵ groups (n=۸): control (saline), lipoppolysacharide (LPS ۲۵۰ mcg/kg bw), and experimental groups (LPS and PMX ۰.۵, ۱, and ۳ mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed. Results: In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX ۱ mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of ۰.۵ and ۱ mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-۱۰ serum levels were elevated by ۱ mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β۱ serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration.Conclusion: In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-۱۰.

کلیدواژه ها:

amyloid ، Cytokines ، Hippocampus ، Lipopolysaccharide ، Neuroinflammation ، Pramipexole