Neurobiology

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Importance of The Study of Microglial Cells in Neurobiology
An important representation of the immune system of the mammal brain is the microglial cells due to the various roles they play in the diseases and injuries to the body. Previously the role they play in a healthy brain was unknown. And details about their involvement in cases of brain damage were scanty. For this reason, it was necessary to probe the mammal brain to explore the intricacies that are microglial cells. Even though the cells seem inactive in their resting state by use of vivo two-photon imaging, researchers found that they are highly active. Upon further exploration of their complex environment the scientist found that the. Microglia plays a great part in the immune system of an adult mammal ADDIN CSL_CITATION { “citationItems” : [ { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/nn1472”, “ISBN” : “1097-6256 (Print)\n1097-6256 (Linking)”, “ISSN” : “10976256”, “PMID” : “15895084”, “abstract” : “Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein-coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes.

The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.”, “author” : [ { “dropping-particle” : “”, “family” : “Davalos”, “given” : “Dimitrios”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Grutzendler”, “given” : “Jaime”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yang”, “given” : “Guang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “V.”, “family” : “Kim”, “given” : “Jiyun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zuo”, “given” : “Yi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jung”, “given” : “Steffen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Littman”, “given” : “Dan R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dustin”, “given” : “Michael L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gan”, “given” : “Wen Biao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } ], “container-title” : “Nature Neuroscience”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : [ [ “2005” ] ] }, “page” : “752-758”, “title” : “ATP mediates rapid microglial response to local brain injury in vivo”, “type” : “article-journal”, “volume” : “8” }, “uris” : [ “http://www.mendeley.com/documents/?uuid=b6e2c233-c526-4281-8098-501db483d5c3” ] } ], “mendeley” : { “formattedCitation” : “(Davalos et al.)”, “plainTextFormattedCitation” : “(Davalos et al.)”, “previouslyFormattedCitation” : “(Davalos et al.)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Davalos et al.).
The role they play is of paramount importance by ensuring that injury and diseases do not harm other organs and body parts. Immediately there are any changes in the blood-brain barrier the cells are quickly transformed from static resting state into ferocious protector to the injured part. This discovery is very important in the research on how the nervous system reacts to disease and injury and it will play a great role in the discovery of pain relief, disease alleviation and eradication. Immunity is an important aspect of the neuroscience. For this reason, this study plays a very important part in neuroscience on the study involving brain injury and the reaction of the microglial in cases of brain injury. As soon as there is an injury to the brain the microglial cell very quickly rushes and surround the injured part rapidly forming a barrier between the injury and the healthy brain matter this reaction ensures that the healthy part remains intact while the injured part either heals of wastes away. The researchers found that this process can be mimicked by locally injecting ATP into the brain ADDIN CSL_CITATION { “citationItems” : [ { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s12272-010-0211-8”, “ISBN” : “8228807848”, “ISSN” : “02536269”, “PMID” : “20195827”, “abstract” : “In response to brain insults, microglia, the resident inflammatory cells in CNS, migrate into injured sites to initiate inflammatory responses in brain. ATP, released from apoptotic or necrotic cells induce chemoattractive responses but the mechanism is not clear yet. In this study, we investigated whether ATP modulates microglial migration by regulating the activity of matrix metalloproteinases (MMPs). ATP induced rapid microglial migration and increased the activity of MMP-9 in the culture supernatants (secreted compartments) in a concentration-dependent manner. The increased activity of secreted MMP-9 is due to the increased protein secretion, but not by the increased MMP-9 mRNA and protein expression. Inhibition of MMP-9 activity by treatment with specific inhibitors including GM6001 and SB-3CT prevented ATP-induced microglial migration. ATP-induced microglial migration was also inhibited by P2Y receptor antagonists including clopidogrel as well as PI3K inhibitor such as wortmanin. Taken together, ATP non-transcriptionally increased MMP-9 activity by activation of P2Y and PI3K. The results from the present investigation may provide further insights into the regulation of the activity of MMP-9 during microglial migration, which may play essential role in the regulation of inflammatory responses in pathological situations such as neurodegenerative disorders.”, “author” : [ { “dropping-particle” : “”, “family” : “Choi”, “given” : “Min Sik”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cho”, “given” : “Kyu Suk”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Shin”, “given” : “Sun Mi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ko”, “given” : “Hyun Myung”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kwon”, “given” : “Kyung Ja”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Shin”, “given” : “Chan Young”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ko”, “given” : “Kwang Ho”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } ], “container-title” : “Archives of Pharmacal Research”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : [ [ “2010” ] ] }, “page” : “257-265”, “title” : “ATP induced microglial cell migration through non-transcriptional activation of matrix metalloproteinase-9”, “type” : “article-journal”, “volume” : “33” }, “uris” : [ “http://www.mendeley.com/documents/?uuid=b28c891d-1fa4-4a6e-8111-75ad3f62fa7a” ] } ], “mendeley” : { “formattedCitation” : “(Choi et al.)”, “plainTextFormattedCitation” : “(Choi et al.)”, “previouslyFormattedCitation” : “(Choi et al.)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Choi et al.).
Due to the delicate nature of the brain cells in the mammals and a slight injury to the brain may lead to the dysfunction on the body part it controls. In cases where the brain part injury is responsible for speech functions, automatically the patient experiences speech impairment. Therefore, this study is extremely important to neuroscience in that it enables the scientists to understand the intricate mechanisms that entail the relationship b between microglial cells and their significance in preventing brain damage in case of injury. Many people have lost their lives and the survivors of brain injury ended up with impaired function of the respective organs. This study is an eye-opener in the care needed to prevent further damage to the healthy part. The study is also important to neuroscientists as it can be used for other related studies in the nervous systems and microglial cells. From the study it is evident that the injection of ATP into the brain cells simulates the same effect on the brain as the microglial reaction during brain injury ADDIN CSL_CITATION { “citationItems” : [ { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1126/science.1110647”, “ISBN” : “1095-9203 (Electronic)\r0036-8075 (Linking)”, “ISSN” : “00368075”, “PMID” : “15831717”, “abstract” : “Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.”, “author” : [ { “dropping-particle” : “”, “family” : “Nimmerjahn”, “given” : “Axel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kirchhoff”, “given” : “Frank”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Helmchen”, “given” : “Fritjof”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } ], “container-title” : “Science”, “id” : “ITEM-1”, “issue” : “5726”, “issued” : { “date-parts” : [ [ “2005” ] ] }, “page” : “1314-1318”, “title” : “Neuroscience: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo”, “type” : “article-journal”, “volume” : “308” }, “uris” : [ “http://www.mendeley.com/documents/?uuid=f9d390d6-de6c-4667-b256-abaf1bd8b613” ] } ], “mendeley” : { “formattedCitation” : “(Nimmerjahn et al.)”, “plainTextFormattedCitation” : “(Nimmerjahn et al.)”, “previouslyFormattedCitation” : “(Nimmerjahn et al.)” }, “properties” : { }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Nimmerjahn et al.). Brain surgery is usually an invasive procedure and due its delicate nature patients have on some occasions emerged from the operation theatre with more damage to the brain than they initially had. From this study neuroscientists can avoid causing damage to the healthy cells and only remove the damaged or injured part.

Works Cited
ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY Choi, Min Sik, et al. “ATP Induced Microglial Cell Migration through Non-Transcriptional Activation of Matrix Metalloproteinase-9.” Archives of Pharmacal Research, vol. 33, no. 2, 2010, pp. 257–65, doi:10.1007/s12272-010-0211-8.
Davalos, Dimitrios, et al. “ATP Mediates Rapid Microglial Response to Local Brain Injury in Vivo.” Nature Neuroscience, vol. 8, no. 6, 2005, pp. 752–58, doi:10.1038/nn1472.
Nimmerjahn, Axel, et al. “Neuroscience: Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo.” Science, vol. 308, no. 5726, 2005, pp. 1314–18, doi:10.1126/science.1110647.