Central Responses to Peripheral Inflammation May Include Decreased Expression of Key Apoptotic Protease Caspase-3 in the Brainstem

Microglia activation by proinflammatory stimuli, includinglipopolysaccharide (LPS), is considered among the risk factors forneurodegeneration, although LPS treatment may also have a neuroprotective effect,necessitating further analysis of the relationship between microglialactivation and cell death regulators. Here, we carried out a comparativeanalysis of the expression of Iba-1, a protein marker for microgliaactivation, and caspase-3, a key executor protease of apoptosis,in the brainstem and prefrontal cortex of Wistar rats, dependingon LPS dose and schedule of its intraperitoneal administration.One day after a single LPS administration at a dose of 0.5 mg/kg,Iba-1 and caspase-3 expression levels were indistinguishable fromcontrol values in both brain structures. A fourfold LPS administrationat the same dose over 7 days (once in 2 days) led to a significantincrease in Iba-1 expression levels in the brainstem one day afterthe last injection, which was accompanied by a significant decreasein caspase-3 expression. In the brainstem, the same effects wereobserved 7 days after a single LPS administration at a higher dose of5 mg/kg. In the frontal cortex, by contrast, no changes in caspase-3expression were found in a 7-day experiment, while Iba-1 expressionrose only following a single LPS administration at 5 mg/kg. The detecteddecrease in caspase-3 expression in the brainstem under neuroinflammatoryconditions may reflect the development of adaptive neuroprotectiveprocesses, particularly important for the brain structure responsiblefor such key body’s functions as respiration, blood pressure, andheartbeat.