Histology of Glial Cells
The term glial cell (more formally referred to as neuroglia) was traditionally used in reference to cells of the central nervous system. Over recent years, the definition of the term has been widened to include all non-neuronal cells that are associated with neurons in both the central and peripheral nervous systems. These cells have the responsibility of maintaining a homeostatic balance, myelinating neurons, providing structural support for neurons, as well as protecting them throughout the nervous system.
Glial cells are smaller, more numerous and are morphologically and functionally different from neuronal cells. Additionally, they do not propagate action potentials. This article will look at glial cells (or glia) in the central and peripheral nervous systems.
Glia of the Central Nervous System
There are four general types of glia in the central nervous system; astrocytes, oligodendrocytes, microglia, and ependymal cells. Some of these cells can be further subdivided based on their embryology.
Oligodendrocytes have long cytoplasmic projections extending from their soma. Their nuclei are small and surrounded by a halo of cytoplasm, rich in polyribosomes and granular endoplasmic reticulum. These cells are distributed in both the grey and white matter of the central nervous system, but more so in the white matter. This cell line can be subdivided into interfascicular oligodendrocytes (between myelinated axons) and satellite oligodendrocytes (adjacent to cell bodies primarily in grey matter).
Oligodendrocytes are responsible for the production of myelin. Myelin is an insulating membranous sheath that is wrapped around the axon along its length. There are regions along the axon that remain unmyelinated, known as nodes of Ranvier. The myelin sheath prevents the random spread of electrical impulses and increases the speed at which these impulses travel (a process known as saltatory conduction). The larger the diameter of the myelin sheath, the greater the conduction velocity of the neuron.
There are star-shaped glial cells that extend numerous processes (end feet) known as astrocytes. The astrocytes are characterized by glial fibrillary acidic proteins (GFAP; intermediate filaments) throughout their cytoplasm. However, in the fetal brain and in the adult grey matter, astrocytes have very few GFAP in their cytoplasm. The extensive branching of these cells allows them to be in contact with the soma (cell body), dendrites and axons of many neurons. The end feet of the astrocytes are an important part of the border between the central nervous system and non-neuronal tissue. It forms the glia limitans on the visceral surface of the pia mater, by joining multiple layers of end feet. The end feet also cover the vasculature of the CNS.
Astrocytes can be further divided into protoplasmic and fibrous subtypes. The protoplasmic astrocytes are located in the grey matter. Protoplasmic (velate) astrocytes have numerous branches that wrap around terminal segments of axons, synapses and dendrites. They have specialized neurotransmitter transporter molecules that aid in terminating action potentials by absorbing the neurotransmitters. Velate astrocytes also have a dense expression of potassium channels that can limit the dissemination of electrical impulses to neighbouring neurons within an axon bundle. Fibrous astrocytes are more commonly found in, and are oriented longitudinally within the plane of the fibre bundles of the white matter. They appear fibrous due to the large amount of GFAP that is found in their cytoplasm. If large amounts of GFAP are found in protoplasmic astrocytes, then a pathological insult might have occurred.
There are other subtypes of astrocytes. These include the pituicytes of the neurohypophysis (posterior pituitary gland), olfactory ensheathing cells of the olfactory nerves and bulbs, and Müller cells of the retina. Astrocytes provide metabolic and structural support, maintain ionic homeostasis in the extracellular fluid and release growth factors to promote neuronal growth. Furthermore, the end-feet processes form the glia limitans, which lines the parietal surface of the brain and spinal cord at its interface with the pia mater. This limits the communication between the CNS and other tissue. The astrocyte end-feet also promote the underlying epithelial cells to form pervasive tight junctions that significantly limit the passage of particular solutes into the CNS (selectively permeable).
The microglial cell population accounts for roughly 5% of the glial population. These cells are small, their nuclei are elongated and their cytoplasm is sparse. The cells are found in both white and grey matter. They originate from the monocyte cell line (specialized macrophage derived from myeloid precursor cells) and act as the immune effector cells of the central nervous system. In healthy individuals, they are considered to be dormant.
Ependymal cells can either be low cuboidal or columnar epithelial cells that cover the cerebral ventricular system. They are further classified as choroidal epithelial cells, ependymocytes or tanycytes.
The choroidal epithelial cells have basal (adjacent to the basement membrane) invagination and apical microvilli. They participate in regulating the chemical contents of cerebrospinal fluid (CSF). The ependymocytes are the most abundant of the three ependymal cell lines. Their apical surfaces also contain microvilli, while their bases have cytoplasmic extensions that integrate with the end feet of astrocytes. These cells are found throughout the ventricular system and permits communication between the CSF and the nearby nervous tissue. Tanycytes are most prominent along the floor of the third ventricle (in the hypothalamus). Their long basal processes extending from the basal surface terminate on the vasculature and pia mater.
Glia of the Peripheral Nervous System
The two major cell types in the peripheral nervous system are Schwann cells and satellite cells. These cells are homologous to the oligodendrocytes and astrocytes of the central nervous system, with very subtle differences.
Schwann cells are analogous to the oligodendrocytes of the central nervous system. They are tubular with stretched nuclei. They are intimately wrapped around the axons of neurons in the peripheral nervous system. One of the differences between oligodendrocytes and Schwann cells is that oligodendrocytes can myelinate multiple neurons at a time, but a single Schwann cell only myelinates one neuron. The axon passes through the cytoplasm of the Schwann cell and is held in place by the mesaxon (double layer of surface membrane). As was the case in the central nervous system, Schwann cells in the peripheral nervous system leave small gaps between bundles of myelin along the axon called nodes of Ranvier.
Nerve fibers with larger diameters have thicker layers of myelin surrounding their axon. Small diameter neurons remain unmyelinated. The degree of myelination is used to classify the nerve fibers into different subtypes. There are type A fibers that are the thickest, with the highest conduction velocity. Type C fibers that are the thinnest and are unmyelinated, and type B fibers that range in between types A and C with regards to both diameter and myelination.
Satellite cells are located both in the central and peripheral nervous systems. While their exact function is unknown, they are found around the soma of neuronal cells in the central nervous system and the ganglia of the peripheral nervous system.
Astrocytic scars are common features of central nervous system injury that cause breakdown of neurons. The scar forms as a result of either hypertrophy or proliferation of astrocytes to fill the spaces left by the cellular destruction. Astrocytes also release interleukin (IL-1), prostaglandins and other immune cells in the face of pathological insults. They work in conjunction with microglia to regulate the inflammatory process in the central nervous system.
Degeneration of clusters of oligodendrocytes, along with their myelinating components, is a key feature of demyelinating diseases (e.g. multiple sclerosis, Guillain-Barré Syndrome, or chronic demyelinating polyneuropathy). The myelin is replaced by plaques, which cause a disruption in the spread of the action potential along the axon. It is possible for remyelination to occur in instances where the neurons survive the insult and oligodendrocyte precursor cells replace the lost myelin.