Neuroglia are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons.[rx] In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia, and in the peripheral nervous system glial cells include Schwann cells and satellite cells. They have four main functions:
- (1) to surround neurons and hold them in place;
- (2) to supply nutrients and oxygen to neurons;
- (3) to insulate one neuron from another;
- (4) to destroy pathogens and remove dead neurons.
They also play a role in neurotransmission and synaptic connections,[rx] and in physiological processes like breathing.[rx][rx][rx] While glia were thought to outnumber neurons by a ratio of 10:1, recent studies using newer methods and reappraisal of historical quantitative evidence suggests an overall ratio of less than 1:1, with substantial variation between different brain tissues.[rx][rx]
Glial cells have far more cellular diversity and functions than neurons, and glial cells can respond to and manipulate neurotransmission in many ways. Additionally, they can affect both the preservation and consolidation of memories.[rx]
Neuroglia of the Central Nervous System
Glia, named from the Greek word for “glue,” support and scaffold neurons while performing other unique functions.
Neuroglia in the CNS include astrocytes, microglial cells, ependymal cells, and oligodendrocytes.
Neuroglia in the PNS includes Schwann cells and satellite cells. Astrocytes support and brace the neurons and anchor them to their nutrient supply lines. They also play an important role in making exchanges between capillaries and neurons.
Microglial cells can transform into a special type of macrophage that can clear up the neuronal debris, while monitoring the health of the neuron.
Ependymal cells are another glial subtype that lines the ventricles of the CNS to help circulate the CSF.
Oligodendrocytes are cells that wrap their process tightly around the fibers producing an insulating covering called the myelin sheath.
Schwann cells are similar in function to oligodendrocytes and microglial cells.
Satellite cells perform a similar function to astrocytes,
myelin: A white, fatty material, composed of lipids and lipoproteins, that surrounds the axons of nerves.
glia: Non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomic nervous system.
astrocyte: a neuroglial cell, in the shape of a star, in the brain
Neuroglia or glial cells, are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the central (CNS) and peripheral nervous systems (PNS). It was long believed that neuroglia did not play any role in neuro-transmission, however recent advances have demonstrated that neuroglia play a key role in synapse formation and maintenance.
Neuroglia of the CNS
Neuroglia in the CNS include astrocytes, microglial cells, ependymal cells, and oligodendrocytes. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas.
- Astrocytes are delicate, star-shaped branching glial cells. Their numerous radiating processes cling to neurons and their synaptic endings. These astrocytes cover nearly all the capillaries in the CNS. They support and brace the neurons and anchor them to their nutrient supply lines. They also play an important role in making exchanges between capillaries and neurons. Astrocytes also regulate the external chemical environment of neurons by removing excess ions and recycling neurotransmitters released during synaptic transmission.
- Microglial cells are small and have thorny processes that can touch the neighboring neurons. Microglial cells can transform into a special type of macrophage that can clear up the neuronal debris. They are also able to monitor the health of neurons by detecting injuries to the neuron.
- Ependymal cells are another glial subtype that line the ventricles of the CNS, forming a permeable barrier between the cerebrospinal fluid (CSF) and underlying cells, and also aid in the circulation of CSF through cilial beat.
- Oligodendrocytes are cells that have fewer processes compared to astrocytes. They line up along the nerve fibers in the CNS and wrap their process tightly around the fibers producing the insulating myelin sheath.
Neuroglia of the PNS
Neuroglia in the PNS include Schwann cells and satellite cells.
- Schwann cells are similar in function to oligodendrocytes and microglial cells, providing myelination to axons in the PNS. They also have phagocytotic activity and clear cellular debris that allows for regrowth of PNS neurons.
- Satellite cells are similar in function to astrocytes small cells that surround neurons in sensory, sympathetic, and parasympathetic ganglia, helping to regulate the external chemical environment. They are highly sensitive to injury and inflammation and appear to contribute to pathological states, such as chronic pain.
Neuroglia of the Peripheral Nervous System
The two kinds of glia cells in the PNS, Schwann cells and satellite cells; each have unique functions.
There are two kinds of neuroglia in the peripheral nervous system (PNS): Schwann cells and satellite cells.
Schwann cells provide myelination to peripheral neurons. Functionally, the Schwann cells are similar to oligodendrocytes of the central nervous system (CNS).
Satellite cells play an important role in modulating the PNS following injury and inflammation. These resemble the astrocytes of the CNS and assist in regulating the external chemical environment.
glia: Non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain and in other parts of the nervous system.
Schwann cells: The principal glia of the PNS, these cells are involved in the conduction of nervous impulses along axons, nerve development and regeneration, trophic support for neurons, production of the nerve extracellular matrix, modulation of neuromuscular synaptic activity, and presentation of antigens to T-lymphocytes.
Satellite glial cells: These cells line the exterior surface of neurons in the PNS and neuron cell bodies within ganglia.
The PNS has two kinds of neuroglia: Schwann cells and satellite cells. Schwann cells provide myelination to peripheral neurons. They also perform phagocytic functions and clear cellular debris, allowing for the regrowth of PNS neurons. Functionally, the Schwann cells are similar to oligodendrocytes of the CNS.
Satellite cells are small glia that surrounds neurons’ sensory ganglia in the ANS. These resemble the astrocytes of the CNS and assist in regulating the external chemical environment. PNS satellite glia is very sensitive to injury and may exacerbate pathological pain.
Neuroglia [rx]are classified into glia of the peripheral nervous system (PNS) and of the CNS. The glial cells of the PNS originate (similarly to peripheral neurons) from the neural crest and are classified into:
- Schwann cells [rx] associated with sensory, motor, sympathetic, and parasympathetic axons; Schwann cells are further subdivided into (i) myelinating Schwann cells that myelinate peripheral axons; (ii) non-myelinating Schwann cells that surround multiple non-myelinating axons and (iii) perisynaptic Schwann cells, which enwrap peripheral synapses and maintain homeostasis in the perisynaptic milieu.
- Satellite glial cells [rx, rx], which are surrounding neurons in sensory, sympathetic, and parasympathetic ganglia. These satellite glial cells control local homeostasis and are capable of reactive remodeling in pathology.
- Olfactory ensheathing cells [rx], which are a part of the olfactory system. These cells extend very fine processes that enclose large numbers of unmyelinated olfactory axons
Enteric glia [rx, rx], represented by homeostatic glial cells of the enteric nervous system.
Neuroglia of the CNS are subdivided into microglia (cells of ectodermal, neuroepithelial origin) and microglia (cells of mesodermal, myeloid origin). The macroglia is further classified into
Astroglia or astrocytes. Astrocytes are a heterogeneous population of primary homeostatic glia residing throughout the brain and the spinal cord, in both grey and white matter. Astroglia include [rx, rx]:
- protoplasmic astrocytes of grey matter;
- fibrous astrocytes of white matter
- surface-associated astrocytes associated with the cortical surface in the posterior prefrontal and amygdaloid cortex;
- Velate astrocytes, which are localized in the parts of the brain that are densely packed with small neurons, for example in the olfactory bulb or in the granular layer of the cerebellar cortex;
- Radial glia, which are the pluripotent neural cells precursors that generally disappear at birth in mammals
- Radial astrocytes, which include Bergmann glia in the cerebellum, Müller glia of the retina, radial glia-like neural stem cells of the neurogenic niches and tanycytes of the hypothalamus, hypophysis and the raphe part of the spinal cord;
- Pituicytes, which are the glial cells of the neurohypophysis;
- Gomori astrocytes rich in iron and positive for Gomori’s chrome alum hematoxylin staining identified in the hypothalamus and in the hippocampus;
- Perivascular and marginal astrocytes, which are placed near the pia mater, where they form endfeet with blood vessels. These astrocytes do not establish contacts with neurons and their main function is in establishing the pial and perivascular glia limitans barriers.
- Ependymocytes, choroid plexus cells, and retinal pigment epithelial cells. These cells line up the ventricles and the subretinal space; the choroid plexus cells produce the cerebrospinal fluid. Ependymocytes possess small movable processes (microvilli and kinocilia), which by rhythmic movements produce a stream of cerebrospinal fluid.
- In addition, the brain of higher primates (including humans) contains several types of specialized astrocytes [rx, rx], which include:
- Interlaminar astrocytes;
- Polarised astrocytes;
- Varicose projection astrocytes.
The function of this hominoid astroglia remains unknown.
Parenchymal astrocytes of the human brain are substantially larger and more complex compared with astroglial cells of rodents and have distinct gene expression patterns [rx–rx, rx, rx]. Human protoplasmic astrocytes have about 10 times more primary processes and a more complex secondary process arborization, with an average volume about 16.5 times larger than that of the corresponding astrocytes in a rat brain [rx]. The larger human protoplasmic astrocytes also have extended outreach onto neuronal structures, on average contacting and encompassing up to 2 million synapses residing within astrocytic territorial domains, significantly more than the integrating capacity of rodent protoplasmic astrocytes, which covers ~20,000–120,000 synaptic contacts [rx, rx]. Similarly, human fibrous astrocytes have a 2.14-fold larger domain compared to that in rodents [rx].
Oligodendroglia or oligodendrocytes, the myelinating cells of the CNS are subdivided into 4 classes [rx]:
- Type I oligodendrocytes are most numerous in the cortex and grey matter; they have small rounded somata and fine branching processes that myelinate 30 or more small diameter axons;
- Type II oligodendrocytes are similar to type I, but have parallel arrays of intermediate length internodes (100–250 μm), and are most common in white matter, such as the corpus callosum, optic nerve, cerebellum, and spinal cord;
- Type III oligodendrocytes have larger (than type I and II) irregular cell bodies, with one or more thick primary processes that myelinate a small number of large diameter axons with long internodes (250–500 μm). These cells are localized in the cerebral and cerebellar peduncles, the medulla oblongata, and the spinal cord funiculi;
- Type IV oligodendrocytes, are somewhat similar to Schwann cells, being directly associated with a large diameter axon to form a single long internodal myelin sheath (as long as 1000 μm), and are restricted to tracts containing the largest diameter axons near the entrance/exit of nerve roots into the CNS.
NG-2 glia also known as oligodendrocyte progenitor cells or OPCs, or synoviocytes, or polydendrocytes [rx, rx]. The NG2 glia can have a homeostatic role and contribute to adulthood myelination, albeit their functions are yet to be better characterized.
Microglia originate from the fetal macrophages that migrate into the neural tube very early in embryonic development; arguably, microglia represent the first parenchymal glia to populate neural tissue in development. Microglial cells carry numerous physiological functions, including shaping neuronal synaptic connectivity, removing of redundant or apoptotic neurons in the development, and regulating synaptic transmission [rx, rx, rx]. Microglia from the main defense system of the CNS through an evolutionarily conserved program of activation (microgliosis) can produce numerous neuroprotective and neurotoxic phenotypes [rx, rx].
Some glial cells function primarily as the physical support for neurons. Others provide nutrients to neurons and regulate the extracellular fluid of the brain, especially surrounding neurons and their synapses. During early embryogenesis, glial cells direct the migration of neurons and produce molecules that modify the growth of axons and dendrites. Some glial cells display regional diversity in the CNS and their functions may vary between the CNS regions.[rx]
Neuron repair and development
Glia is crucial in the development of the nervous system and in processes such as synaptic plasticity and synaptogenesis. Glia has a role in the regulation of repair of neurons after injury. In the central nervous system (CNS), glia suppresses repair. Glial cells known as astrocytes enlarge and proliferate to form a scar and produce inhibitory molecules that inhibit the regrowth of a damaged or severed axon. In the peripheral nervous system (PNS), glial cells known as Schwann cells (or also as neuro-hemocytes) promote repair. After the axonal injury, Schwann cells regress to an earlier developmental state to encourage regrowth of the axon. This difference between the CNS and the PNS raises hopes for the regeneration of nervous tissue in the CNS. For example, a spinal cord may be able be repaired following injury or severance.
Myelin sheath creation
Oligodendrocytes are found in the CNS and resemble an octopus: they have bulbous cell bodies with up to fifteen arm-like processes. Each process reaches out to an axon and spirals around it, creating a myelin sheath. The myelin sheath insulates the nerve fiber from the extracellular fluid and speeds up signal conduction along with the nerve fiber.[rx] In the peripheral nervous system, Schwann cells are responsible for myelin production. These cells envelop nerve fibers of the PNS by winding repeatedly around them. This process creates a myelin sheath, which not only aids in conductivity but also assists in the regeneration of damaged fibers.
Astrocytes are crucial participants in the tripartite synapse. They have several crucial functions, including clearance of neurotransmitters from within the synaptic cleft, which aids in distinguishing between separate action potentials and prevents toxic build-up of certain neurotransmitters such as glutamate, which would otherwise lead to excitotoxicity. Furthermore, astrocytes release gliotransmitters such as glutamate, ATP, and D-serine in response to stimulation.[rx]