Last Updated on August 21, 2020 by Sagar Aryal
The central nervous system (CNS) has a microglial cell as a primary defense mechanism. Microglia originate from primitive macrophages of the yolk sac. In CNS parenchyma microglia contribute 10% of total glial cells population. They are natives of CNS and equally disseminated within the brain and spinal cord. They are prime cells for supporting brain functions and cleanup of infecting agents (bacteria, viruses, etc.). They also clear debris formation from plaques of neurons. They are the most efficient cells as well as profound for minor pathological changes in CNS.
The CNS system is not directly accessed by microbes or microbial agents due to the protective layer of endothelial cells known as the blood-brain barrier (BBB). This barrier inhibits the reaching of infecting agents to the most delicate tissues of the nervous system. Infections occur in-case of direct contact or crossing of BBB.
Microglia derivation and dispersion
During embryogenesis microglia derived from the yolk sac and move to the central nervous system. These cells proliferate and spread in the overall central nervous system. They display a number of structural features, electrophysiological content, membrane conformation, and gene transcription depending on the initiation profile. Their expression profile found to be conserved in different regions of the brain with respect to immune functions, inflammatory signals, and homeostasis.
Forms of Microglia
Microglia are highly flexible cells found in the body and change shape according to requirement. This plasticity is helpful for performing various functions by these cells. They attain a particular structure in response to chemotactic signals or phenotypic response.
Functions of glial cells
These cells release different chemokines, cytokines, reactive oxygen species, reactive nitrogen species, and also prostaglandins in the reaction of injury or invading pathogen. And they secrete anti-inflammatory substances also to reduce inflammation.
Microglial Antigen exhibition
The immediate immune response launch only by microglia inhabitant of CNS. Antigen presentation requires MHC class II molecule expression which is control via a number of substances. MHC class II stimulators are varying such INF-γ is a potential candidate as a stimulator. Expression of MHC II induces t-cell propagation and production of IL-2 and INF-γ from Th1 cells. And IL-4 produces by Th2.
Inflammatory and anti-inflammatory cytokine generation
Diverse immune mediators and inflammatory molecules triggered in different conditions such as infections, neurodegenerative diseases, autoimmune disorders, and chronic inflammation. Cytokines are secreted in innate and adaptive immune response which varies with the diseases and intensity of diseases. Microglia are prime cells regulating inflammatory and immune cytokines in CNS.
Microglial cells generate IL-1 and TNF-α during inflammation of the central nervous system. Antigen or a part of an antigen is potentially inducing these cytokines such as LPS. IL-1 and TNF-α produce inflammation in CNS by disturbing BBB, adhesion molecules, chemokines from astrocytes and endothelial cells. These events promote the entry of leukocytes in the central nervous system.
Microglial anti-inflammatory activity
Anti-inflammatory cytokines are also produced by microglia for example TGF-β, IL-10, and IL-1 antagonistic receptor. IL-10 and TGF-β prevent stimulation of microglial cells for the production of cytokines, reactive oxygen molecules, chemokines, and antigen presentation also prevented by these cytokines. And an antagonistic receptor of IL-1 counteracts by binding to IL-1.
Brain parenchyma is constantly checked by microglial cells and performs trimming of synaptic connections, consuming immune monitoring pathways. These cells mediate physical contact with synapses in response to neuronal stimulations. These actions contribute to neural network refinement which is helpful in learning and memorizing process.
Apoptotic cell elimination
In the nervous system, apoptotic cells are continuously producing during growing and homeostasis and these cells are eliminated by engulfment through microglia. Recognition of apoptotic cells is difficult due to their quick removal from the body. The expression of TREM2, CD11, TIM-4 receptors signals phagocytic cells to engulf apoptotic neurons.
Microglia significance in aging
Myelin breakdown and synapse loss raised with the aging of cells. Studies suggest that with progressive aging synapse loss occurs via complement system and microglial operations. The Amount of C1q proteins increased in the aged brain and myelin degeneration leads to debris formation which regularly removed by phagocytosis. While aging debris clearance started affecting and accumulation of debris causes malfunctioning in neuronal signaling, memory loss, etc.
Neurodegenerative role of microglia
Microglia have the potential to kill neurons against a stimulus from the body which leads to neuroinflammation, Alzheimer’s, Parkinson’s, Huntington’s, and prion disease. Microglia contribute to neurodegeneration by secreting pro-inflammatory molecules. Signaling pathways that lead to disease formation involves Trem2, Cx3cr1, and progranulin systems. These are protected barriers that regulate the inflammatory reaction of microglial cells and catch harmful stimuli receptors to develop an injury. Neurodegeneration occurs due to inequity in cells functioning of glial cells and treatment could be their control or correction.
Alzheimer’s disease and Microglia functioning
Alzheimer’s disease occurs due to the formation and aggregation of amyloid-beta proteins (senile plaques) and twisted neuronal fibers in CNS. Alzheimer’s disease formation stimulated by microglial pathways and know determined as genetic and transcriptomic connections in microglial function and disease advancement. It is contemplated that astroglial and microglial initiation is a marker of disease and they interrelate with accumulated proteins which eventually cause faulty signaling and death of neurons.
Therapy for neurodegenerative disorders
Treatment of neurodegenerative diseases could be inhibition of activating microglial cells as their prolonged activation causes a neurotoxic impact on CNS. If neuroinflammation prevented or reduced it can slow down disease progression. This could be useful in pharmaceutics to design or investigate microglial inhibitors to cure neurodegeneration.