Abstract
Some mechanisms of neuronal degeneration in endotoxinemia are already well described, but need to be detailed. In this study, we tested the effect of a single intraperitoneal injection of a LPS sub-septic dose (1 mg/kg of animal weight) on calpain activity in the striatum and hippocampus. We showed, that in the hippocampus the day after LPS administration an increase in production of IL-1β and TNF-α mRNA, followed by elevated mRNA expression and activity of µ- and m-calpains without signs of microglia activation is observed. In striatal cells, the day after LPS injection an increase in expression of IL-1β, TNF-α, IBA-1, m-calpain and calpastatin mRNA is revealed, which only intensifies over time. The elicited changes are accompanied by a decrease in motor behavior, which can be considered as a sign of sickness behavior. In the hippocampus, 180 days after LPS administration expression of TNF-α, content and activity of µ-calpain are increased. In the striatum, elevation in expression of TNF-α, IBA-1, µ- and m-calpain mRNA, with hyperactivation of only m-calpain, is observed. Significantly reduced motor activity can be a consequence of LPS-induced neuronal death. A long-lasting endotoxin activates microglia that damage neurons via proinflammation cytokines and calpain hyperactivation. The endotoxin hypothesis of neurodegeneration is unproven, but if correct, then neurodegeneration may be reduced by decreasing endotoxin-induced neuroinflammation and m-calpain hyperactivation. Therefore, the drugs, that decrease endotoxin-induced neuroinflammation and differently inhibit µ- or m-calpain, can be used to prevent or reduce the severity of neurodegeneration.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Maystrenko V.A.: significant input on experimental design, performed animal dosing and sacrifice, tissue processing, PCR, behavior analysis;
Ivleva I.S.: significant input on experimental design, PCR, behavior analysis;
Krytskaya D.U.: significant input on experimental design, calpain activity analysis;
Zubov A.S.: significant input involved in writing revisions and interpretation experimental results;
Ivlev A.P.: significant input involved in writing revisions and generating figures for the manuscript, developed methods for data analysis;
Karpenko M.N.: significant input on experiment design, significant input as an author, interpretation experimental results and editing of manuscript.
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Maystrenko, V., Ivleva, I., Krytskaya, D. et al. Changes in activity of µ- and m-calpains and signs of neuroinflammation in the hippocampus and striatum of rats after single intraperitoneal injection of subseptic dose of endotoxin. Metab Brain Dis 36, 1917–1928 (2021). https://doi.org/10.1007/s11011-021-00755-y
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DOI: https://doi.org/10.1007/s11011-021-00755-y