D. Dongshu, H. Li, W. Jiaxiang et al. (2017)
There are a lot of interconnected networks that control blood pressure. The Rostral ventrolateral medulla (RVLM) is a main regulator of sympathetic nerve activity and is an important monitor of cardiovascular health problems. Microglia are neuroinflammatory cells within the central nervous system that regulate inflammatory events such as cardiovascular disease. This study examines the role of microglia during neuroinflammation.
Rats were divided into three groups: A control group, a chronically stressed group, and a chronically stressed group given minocycline, which is a microglia activation inhibitor. To produce the stress environment, rats were placed inside a cage containing floors that delivered randomized shocks and a buzzer to accompany the shocks.
The chronically stressed rats showed increased blood pressure, which may be caused by the elevated levels of norepinephrine (NE), glutamate, and decreased levels of GABA that were measured. Ionized calcium-binding adapter molecule -1 (Iba-1) is a protein that is expressed in microglia. Chronic stress was shown to significantly increase Iba-1 levels in SIH rats. About 10% of microglia were active in control rats, while 40-50% were active in stressed rats. Pro-inflammatory cytokine (PIC) levels were also increased in chronically stressed rats when compared to non-stressed rats. Although autophagic vacuoles are found in small numbers within the RVLM of control rats, the concentration was shown to double within chronically stressed rats. Autophagic markers LC3 and p62 were also shown to increase in chronically stressed rats. RVLM neurons typically show low levels of autophagic flux, which is a measure of autophagic degradation activity, but chronically stressed rats exhibited a significantly elevated autophagic flux.
A third group, that received minocycline, expressed much lower levels of PICs when compared to the untreated stressed group. What was interesting was that expression of TNF-alpha within the RVLM in stressed rats treated with minocycline was actually lower that the control group. Although the minocycline treated stressed group still showed elevated levels of NE and glutamate, it was still significantly lower than the untreated stressed groups. When treated with minocycline, the stressed rats showed lower levels of autophagic flux when compared to untreated stressed group, even though it was still significantly higher than the control group
They concluded that the microglia activate and release PICs, which causes the increases RVLM sympathetic nerve activity. Minocycline was also found to decrease the overall sympathetic output from the RVLM and increase the autophagic flux of stressed rats. I chose this article after finishing up my blog post about microglia from last week. I’m beginning to learn just how big of a role microglia play in the equilibrium and immune defense of the brain. Although we are not examining microglia in the lab currently, it would be fascinating to see the activation levels during the microinjection trials.
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