Microglia and brain macrophages: An update

Abstract

Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means “neuroinflammation” is absurd and misleading. Neuropathologists are in the best position to provide clarity to end the existing confusion. The functions of microglia in the non‐diseased brain probably include a role in synaptic maintenance, but defects in the expression of specific molecules on microglia can also cause leukoencephalopathy, such as Nasu‐Hakola disease (NHD) and hereditary leukoencephalopathy with spheroids (HDLS). “Microgliopathies” is a new term used to designate conditions where microglial dysfunction is primary and at the center of the disease process. The molecules responsible are DAP12 or TREM2 in NHD and CSF1R in HDLS, respectively, but further studies are needed to clarify how exactly these microglial molecules influence the pathogenesis of axonal and myelin loss. Diffusely infiltrating glial tumors showing microglial differentiation (true microglioma) are exceedingly rare but recent evidence suggests that they indeed exist, although their molecular genetic characterization is still lacking. Participation of the expert neuropathology community will be required to identify additional cases and provide the latter. A large number of tumor‐associated macrophages (TAMs), which are partly derived from microglia, have been observed in glioblastomas. In TAMs, the expression of M2‐like molecules is higher than that of M1‐like molecules, but the number and differentiation state of TAMs vary in the intratumoral area and with the type of macrophage markers used. In future studies, we should focus on the morphological and molecular alterations of the microglia that are specific to the disease where they are observed.

Genetic dissection of oligodendroglial and neuronalPlp1function in a novel mouse model of spastic paraplegia type 2

“…Axonal damage is commonly associated with microgliosis, that is, an increased density and “activation” of microglial cells (Sasaki, ). We therefore immunolabeled microglia using antibodies against allograft‐inflammatory factor (AIF1/IBA1) (Figure a–e) and lysosomal‐associated membrane protein 2 (LAMP2/MAC3) (Figure g–k) and quantified the relative area occupied by immunostaining (Figure f,l).…”

Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation

“…Microglia are the brain resident macrophages and play a major role in the development of brain inflammation and pathology (Ransohoff, 2016; Sasaki, 2016). Accordingly, the effect of inflammatory mediators relevant to alcohol-induced brain inflammation, ethanol, LPS, Tnfα and Hmgb1, on microglial Pde4 expression was examined.…”

Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease

“…27,28 TREM2 is implicated in the regulation of a regulatory microglial response. 44 TREM2 loss of function results in reduced microglial phagocytosis, [30][31][32] while TREM2 function inhibits inflammatory responses in microglia via suppression of NF-kB pathways and is strongly implicated in microglia innate immunity. 29 Overexpression of TREM2 reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuropathology including DA neuron degeneration and neuroinflammation by negatively regulating NF-κB signaling pathways in mice.…”