Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation

Ligation of antigen receptors at the surface of lymphocytes initiates a transcriptional and translational response that is required for cellular proliferation and effector function. By contrast, co-stimulatory-molecule ligation contributes to the immune response by allowing the uptake and utilization of extracellular nutrients to provide energy for cellular proliferation and effector functions. Growth factors also potentiate the ability of lymphocytes to metabolically switch between resting and proliferative states. Lymphocytes that do not receive these signals fail to increase their metabolism to meet the higher bioenergetic demands of cell growth and are either deleted or rendered unresponsive to mitogenic signals. In this Review, we describe how T cells actively acquire metabolic substrates from their environment to meet these energy demands and respond appropriately to pathogens.

Fuel feeds function: energy metabolism and the T-cell response.

mTOR is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental cues in the form of growth factors, amino acids, and energy. In the study of the immune system, mTOR is emerging as a critical regulator of immune function because of its role in sensing and integrating cues from the immune microenvironment. With the greater appreciation of cellular metabolism as an important regulator of immune cell function, mTOR is proving to be a vital link between immune function and metabolism. In this review, we discuss the ability of mTOR to direct the adaptive immune response. Specifically, we focus on the role of mTOR in promoting differentiation, activation, and function in T cells, B cells, and antigen-presenting cells.

Regulation of Immune Responses by mTOR

https://discovery.dundee.ac.uk/ws/files/10932724/DGH_TICB_2016.pdf

AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs.

Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.

Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-α production through inhibition of PI 3-kinase/Akt and NF-κB activation in murine BV2 microglial cells

Oleic acid reduces lipopolysaccharide-induced expression of iNOS and COX-2 in BV2 murine microglial cells: possible involvement of reactive oxygen species, p38 MAPK, and IKK/NF-kappaB signaling pathways.

Jung Yeon Lee

Papers

Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.

Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-α production through inhibition of PI 3-kinase/Akt and NF-κB activation in murine BV2 microglial cells

Oleic acid reduces lipopolysaccharide-induced expression of iNOS and COX-2 in BV2 murine microglial cells: possible involvement of reactive oxygen species, p38 MAPK, and IKK/NF-kappaB signaling pathways.

Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-κB activation in BV2 murine microglial cells

Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis.