Accepted Manuscripts                   Back to the articles list | Back to browse issues page

XML Print

Abstract:   (432 Views)
Introduction: Toll-like receptor (TLR) 4 is involved in neuroinflammatory processes in peripheral tissues and central nervous system. Pro-inflammatory cytokines production, due to over activation of TLR4, interfere with insulin signaling elements lead to insulin resistance. Regarding the critical roles of TLR4 and insulin in the pathogenesis of Parkinson’s disease (PD), in the present study the TLR4/insulin receptor interaction was assessed in a neuroinflammation model of PD.
Methods: LPS was injected in the right striatum of male Wistar rats (20µg/rat). Insulin (2.5IU/day), insulin receptor antagonist (S961; 6.5nM/kg) or TLR4 antibody (Resatorvid (TAK242); 0.01µg/rat) were administered intracerebroventricular (ICV) for 14 days. Insulin and TAK242 were also simultaneously injected in a distinct group. Behavioral assessments were performed using rotarod, apomorphine-induced rotation and cylinder tests. The levels of α-synuclein, TLR4 and the elements of insulin signaling pathway were measured in the striatum.
Results: LPS impaired motor performance of the animals, and increased the levels of α-synuclein and TLR4. Furthermore, it reduced mRNA levels of IRS1 and IRS2 and enhanced GSK3β mRNA and protein levels, indicating the development of insulin resistance. Treatment with insulin and TAK 242 improved motor deficits, restored insulin signaling pathway and reduced α-synuclein and TLR4 levels.
Conclusion: The findings indicate that LPS impaired motor function via, at least in part, α-synuclein and TLR4 overexpression and insulin resistance. TLR4 suppression and insulin receptor activation attenuated motor deficits, suggesting TLR4 and insulin receptors are good therapeutic targets for PD modification.

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.