The central nervous system (CNS) is composed of highly specialized cells, each playing a key role in the processing of sensory and motor inputs. Neurons, one CNS cell type, have an anatomy that specializes in the transmission and processing of electrical signals. Detection and expression of mature neurons plays an important role in understanding the health of the CNS and can be accomplished by observing the expression of MAP2, NeuN, Neurofilament-H, Neurofilament-L and Neurofilament-M.
Evidence suggests that aggregated proteins or long-term stimuli can result in chronic inflammation that is harmful to cells and may contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).
In order to maintain proper function, the nervous system is composed of not only neurons, but also supporting non-neuronal cell types such as microglia, oligodendrocytes, and astrocytes.
Microglia are immune cells that are of myeloid origin and migrate to the CNS during development. The many functions of microglia include pruning of complex neural networks during embryogenesis, assisting in synaptic plasticity or preventing excitotoxicity by responding to neurotransmitter release, and mounting an inflammatory response to an acute infection or trauma to the brain. Specific markers for identification of these resident macrophages of the CNS are integrin alpha M (ITGAM/CD11b), the surface glycoprotein F4/80, CD45, iba1, and TMEM119.
In disease states, distinct microglial populations can be identified by molecular signatures called disease-associated microglia (DAMs). DAMs mature in stages, both of which can be characterized by different biomarker expression: Stage 1 DAM microglia upregulate triggering receptor expressed on myeloid cells 2 (TREM2), ApoE, and Dap12, and downregulate P2ry12 and transmembrane protein 119 (TMEM119). Stage 2 DAMs upregulate osteopontin (Spp1) and cystatin 7 (CST7).
Oligodendrocytes are a specialized glial cell type in CNS that produce myelin, which provides a protective sheath to the axons and improves the conduction velocity of signals between neurons. Oligodendrocytes are characterized by the expression of the myelin family proteins: myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), and Myelin Basic Protein (MBP).
Oligodendrocyte progenitor cells exist in the brain to facilitate regeneration of cells due to injury. However, breakdown of myelin and the inability to regenerate oligodendrocytes with insufficient or dysfunctional myelin have been correlated with the pathogenesis of several neurodegenerative diseases including AD, PD, ALS, and multiple sclerosis (MS).
Astrocytes are another immunocompetent glial cell that arise within the CNS and are found within the brain. The most specific markers of astrocytes are GFAP and S100β.
In a healthy nervous system, astrocytes play essential roles in development, regulation of blood flow (by supporting endothelial cells in the blood brain barrier), synaptic transmission and function, and energy and metabolism (by providing nutrients to neurons and synthesizing certain neurotransmitters).
The loss or abnormal function of astrocytes has been implicated in a wide variety of neurodegenerative disease processes. Chronic activation of astrocytes results in the formation of lesions similar to those observed in AD and HD.
Learn more about neurodegeneration and neurodegenerative diseases.