E. Myfanwy Cohen, Suja Mohammed, Mary Kavurma, Polina E. Nedoboy, Sian Cartland, Melissa M.J. Farnham, Paul M. Pilowsky. Autonomic Neuroscience: Basic and Clinical (2019).
Glial cells are cells of the central and peripheral nervous system that are not neurons. One type of glial cell, called microglia, act as a clean-up crew for the central nervous system. Microglia are macrophages that maintain the brain by looking for damage to the neurons or infectious chemicals. Since microglia look for damaged neurons, they also regulate inflammation in the brain. This study focuses on the microglia within a part of the brainstem called the rostral ventrolateral medulla (RVLM), which contributes to the control of blood pressure. The goal of the study was to determine if chronic high blood pressure is associated with a decrease in microglia function in the RVLM.
Fifteen week old spontaneously hypertensive rats (SHRs) and wild type rats were used in this experiment. Blood pressure was taken using a tail cuff to determine if the rats were hypertensive. The brainstems were removed and then placed in the freezer. The frozen brainstems were sectioned and the RVLM and the facial nucleus were punched out. Anti-Iba1 and donkey anti-rabbit AlexaFluor488 were used in the fluorescent tests. At the end of the experiment, rats were euthanized with sodium pentobarbitone.
A significant difference in systolic blood pressure was measured to demonstrate the two distinct groups. The SHRs exhibited a significant higher blood pressure (195 ±8 mmHg) than the wild type rats (144 ±8 mmHg). Two G-coupled protein receptors involved in the normal function of microglia, P2Y12R and CX3CR1, were measured and compared between the two groups of rats. In the RVLM, P2Y12R expression was significantly lower in SHRs by about 37% when compared to the wild type rats. Expression of P2Y12R was also measured in the facial nucleus and exhibited no significant difference between SHRs and the wild type rats. Expression of CX3CR1 was then measured in the RVLM and the facial nucleus. In the RVLM, CX3CR1 expression was shown to be 30.9% lower in the SHRs when compared to the wild type. Expression of CX3CR1 in the facial nucleus was not significantly different between SHRs and the wild type.
The enzyme phenylethanolamine N-methyltransferase (PNMT) is found in the adrenal medulla and plays a role in converting noradrenaline to adrenaline. This allows PNMT to be a marker for adrenergic neurons, which are found in the RVLM but not the facial nucleus. The expression of PNMT was then compared between SHRs and wild type rats. The RVLM exhibited a significant amount of PNMT mRNA, while the facial nucleus showed a very small amount, which verifies the tissue punches have the correct sites.
Researches then observed the differences in microglia cell density between SHRs and wild types rats. The SHRs exhibited 22.9% lower cell density than the wild type. To further observe how active the microglia were, branch length, endpoints, and branch number were also examined. While the number of endpoints and branch numbers did not show a significant difference, branch length was significantly lower in the SHRs when compared to the wild type.
In conclusion, the G-coupled receptors CX3CR1 and P2Y12R play a major role in the normal function of microglia. Spontaneously hypertensive rats exhibit decreased expression of P2Y12R which may lead to the decreased microglia cell density in the RVLM. The researchers do state in the article that more research needs to be done to determine if the change in microglia are the cause or effect of over-activation of the RVLM and exactly how the microglia are being affected. I found this article interesting to our lab work because we constantly discuss the increased activation of RVLM but may not think about the exact repair mechanisms involved that may also not be working properly.
No comments:
Post a Comment