What Are Glial Cells? Types and Functions

Introduction

Neurons receive, process, and transmit information, but they cannot maintain the nervous system by themselves. They depend on several types of cells collectively known as glial cells.

Glial cells regulate the chemical environment around neurons, form myelin, support synapses, participate in immune defense, guide nervous-system development, and respond to injury. They were once regarded mainly as passive support cells, but research now shows that glia are active participants in nervous-system function.

Glial cells, also called glia or neuroglia, are non-neuronal cells that maintain, protect, and regulate the nervous system.

The major glial cells include:

Astrocytes, which regulate the environment around neurons and synapses
Oligodendrocytes, which form myelin in the central nervous system
Microglia, which act as resident immune cells in the central nervous system
Ependymal cells, which line the brain’s ventricles and the spinal cord’s central canal
Schwann cells, which form myelin around peripheral nerves
Satellite glial cells, which surround neuron cell bodies in peripheral ganglia

Glia do much more than hold neurons together. Normal neural signaling depends on continuous communication between neurons and glial cells.

What Are Glial Cells?

Glial cells are specialized cells found throughout the central nervous system (CNS) and peripheral nervous system (PNS).

The CNS consists of the brain and spinal cord. Its principal glial cell categories include astrocytes, oligodendrocytes, microglia, and ependymal cells. The PNS contains Schwann cells, satellite glial cells, enteric glia, and other specialized glial populations.

Most mature glial cells do not transmit information through long-distance action potentials in the same way that neurons do. However, glia are not electrically or chemically inactive. They respond to neurotransmitters, changes in ion concentrations, tissue damage, and signals from other cells. Some communicate through calcium signaling and release molecules that influence nearby cells.

Are Glial Cells More Numerous Than Neurons?

The claim that glial cells outnumber neurons by 10 to 1 throughout the human brain is outdated.

Modern cell-counting studies suggest that the adult human brain contains roughly comparable total numbers of neuronal and non-neuronal cells. However, the ratio varies greatly among brain regions.[1]

The cerebellum contains an especially large number of neurons, while some areas of the cerebral cortex and white matter contain proportionally more glial cells. Therefore, no single glia-to-neuron ratio accurately describes every part of the brain.

What Are the Main Types of Glial Cells?

Glial Cells in the Central Nervous System

Cell type	Location	Principal functions
Astrocytes	Brain and spinal cord	Regulate ions and neurotransmitters, support metabolism, maintain synapses and blood vessels
Oligodendrocytes	Brain and spinal cord	Form CNS myelin around axons
Microglia	Brain and spinal cord	Immune surveillance, debris removal, responses to injury and disease
Ependymal cells	Ventricles and central canal	Line fluid-filled spaces and help regulate cerebrospinal fluid
Radial glia	Mainly developing nervous system	Produce neural cells and guide neuronal migration
Oligodendrocyte precursor cells	Brain and spinal cord	Generate new oligodendrocytes and participate in local signaling

Glial Cells in the Peripheral Nervous System

Cell type	Location	Principal functions
Schwann cells	Peripheral nerves	Form myelin and support peripheral axons
Satellite glial cells	Sensory and autonomic ganglia	Surround neuron cell bodies and regulate their local environment
Enteric glial cells	Enteric nervous system	Support neural circuits and tissue homeostasis in the digestive tract

What Do Astrocytes Do?

Astrocytes are star-shaped glial cells found throughout the brain and spinal cord. Their many processes contact neurons, synapses, blood vessels, and other glial cells.

Regulating the Extracellular Environment

Neural signaling requires tightly controlled concentrations of ions around neurons. Astrocytes help regulate extracellular potassium and other substances that change during neuronal activity.

Astrocytes also remove neurotransmitters, including glutamate, from the space surrounding synapses. This helps limit excessive receptor activation and prepares the synapse for future signaling.

Supporting Neuronal Metabolism

Astrocytes take up nutrients from the bloodstream and participate in the metabolic support of neurons. They store glycogen and can provide metabolic substrates when neural activity increases.

The details of energy exchange between astrocytes and neurons remain an active area of research. It is therefore too simple to describe astrocytes merely as cells that “feed neurons.”

Supporting Synapses

Astrocytes contact large numbers of synapses and can influence:

Synapse formation
Neurotransmitter clearance
Ion balance
Synaptic maintenance
Some forms of synaptic plasticity

The concept of a tripartite synapse emphasizes interactions among the presynaptic neuron, postsynaptic neuron, and surrounding astrocytic processes. However, astrocyte involvement differs among brain regions and synapse types.

Supporting the Blood–Brain Barrier

Astrocytic endfeet closely surround many CNS blood vessels and help maintain the environment needed for blood–brain barrier function.

The barrier itself is formed primarily by tight junctions between specialized endothelial cells. Astrocytes support and regulate the barrier but do not create its principal physical seal.

Responding to Injury

After infection, trauma, stroke, or other CNS damage, astrocytes can undergo reactive astrogliosis. Their structure, gene expression, and activity change as they respond to the damaged tissue.

Reactive astrocytes may help contain injury, restore the extracellular environment, and protect surviving tissue. In some settings, however, glial scarring and other responses may also limit axon regeneration. These effects depend on the type, severity, and timing of the injury.

What Do Oligodendrocytes Do?

Oligodendrocytes produce myelin in the brain and spinal cord.

Myelin is a lipid-rich membrane that wraps around segments of certain axons. It reduces current loss and allows action potentials to travel rapidly between gaps called nodes of Ranvier. This pattern is known as saltatory conduction.

A single oligodendrocyte can extend several processes and myelinate segments of multiple axons. This differs from a myelinating Schwann cell, which normally forms one myelin segment around one peripheral axon.

Oligodendrocytes also provide metabolic and structural support to axons. Therefore, damage to oligodendrocytes can disrupt axonal function as well as myelin.

What Do Microglia Do?

Microglia are the principal resident immune cells of the central nervous system.

Unlike astrocytes and oligodendrocytes, microglia do not arise from the neural tube. Most resident microglia originate from early embryonic myeloid precursors associated with the yolk sac and enter the developing nervous system before birth.[2]

Immune Surveillance

Microglia continuously extend and retract their processes to monitor the surrounding tissue. The older term “resting microglia” can be misleading because microglia remain active even when there is no injury.

Responses to Damage and Infection

When tissue conditions change, microglia can alter their shape, movement, gene expression, and function. Depending on the situation, they may:

Remove damaged cells and cellular debris
Detect pathogens or tissue injury
Release inflammatory or regulatory molecules
Communicate with neurons and other glia
Participate in tissue repair

Microglial responses are diverse and cannot always be divided accurately into simple “good” and “bad” activation states.

Brain Development and Synaptic Remodeling

Microglia also participate in normal brain development. They interact with developing neural cells and contribute to the remodeling of synaptic connections.

This does not mean microglia independently decide which memories or connections should remain. Synaptic remodeling results from interactions among neural activity, molecular signals, microglia, astrocytes, and other cells.

What Do Ependymal Cells Do?

Ependymal cells form a cellular lining along the brain’s ventricles and the central canal of the spinal cord.

Many ependymal cells have cilia that help move cerebrospinal fluid along ventricular surfaces. Specialized ependymal-related cells are also associated with the choroid plexus, where cerebrospinal fluid is produced by a structure containing specialized epithelial cells, blood vessels, and connective tissue.

It is more accurate to say that ependymal cells participate in the ventricular and cerebrospinal-fluid system than to claim that ordinary ependymal cells alone produce all cerebrospinal fluid.

What Do Schwann Cells Do?

Schwann cells are the principal glial cells associated with peripheral nerves.

Myelinating Schwann Cells

A myelinating Schwann cell wraps its membrane repeatedly around a segment of one peripheral axon. The resulting myelin increases the speed and efficiency of action-potential conduction.

Nonmyelinating Schwann Cells

Not all peripheral axons are myelinated. Nonmyelinating Schwann cells surround and support groups of small axons without forming compact myelin around each one.

Peripheral Nerve Repair

After peripheral nerve injury, Schwann cells can change their behavior, help remove damaged material, and create an environment that supports axonal regrowth.

Peripheral axon regeneration is still affected by the location and severity of injury, the distance to the target, scar formation, and whether the axon can reconnect with the correct tissue. Schwann cells do not guarantee full recovery.

What Do Satellite Glial Cells Do?

Satellite glial cells surround neuron cell bodies in sensory and autonomic ganglia outside the brain and spinal cord.

They help regulate the local chemical environment around these neurons and participate in metabolic support and cellular signaling. Changes in satellite glial cells are being studied in relation to persistent pain and peripheral nerve disorders, although many mechanisms remain under investigation.

What Are Radial Glial Cells?

Radial glial cells are especially important during embryonic brain development.

They perform two major roles:

They act as progenitor cells that generate neurons and several types of glia.
Their long processes provide pathways along which newly formed neurons can migrate toward their developing locations.

Some specialized radial glia remain in the mature nervous system, including Bergmann glia in the cerebellum and Müller glia in the retina.

How Do Glial Cells Communicate With Neurons?

Neuron–glia communication is bidirectional.

Neuronal activity changes extracellular neurotransmitter and ion concentrations. Glial cells detect these changes and respond by adjusting ion balance, clearing neurotransmitters, altering metabolic support, modifying myelin, or releasing signaling molecules.

Glial cells can also communicate with one another through:

Chemical messengers
Gap junctions
Calcium signals
Contact-dependent signals
Cytokines and growth factors

The response depends on the glial cell type, brain region, developmental stage, and physiological condition. Glia should therefore not be treated as one uniform cell population.

Why Are Glial Cells Important?

Glial cells are essential because neural circuits require a stable and adaptable cellular environment.

Their combined functions include:

Maintaining ion and neurotransmitter balance
Supporting neuronal energy metabolism
Forming and maintaining myelin
Regulating synapse formation and function
Supporting blood vessels and fluid interfaces
Guiding nervous-system development
Monitoring for infection and tissue damage
Removing cellular debris
Coordinating responses to injury
Supporting peripheral nerve regeneration

A neuron may generate electrical signals, but it cannot function normally without glial regulation.

Clinical Relevance

Glial dysfunction contributes to many neurological diseases, although glia are rarely the only cells involved.

Multiple Sclerosis

In multiple sclerosis, immune-mediated inflammation damages CNS myelin and oligodendrocytes. This disrupts signal conduction and may eventually contribute to axonal injury.

Peripheral Demyelinating Disorders

Damage to Schwann cells or peripheral myelin occurs in conditions such as Guillain–Barré syndrome and some inherited neuropathies.

Gliomas

Gliomas are tumors classified according to features resembling particular glial lineages. Major categories include astrocytomas, oligodendrogliomas, and ependymomas.

Modern tumor classification uses molecular and genetic findings in addition to microscopic appearance. A tumor’s name does not necessarily mean that it arose directly from a fully mature glial cell of the same name.

Neurodegenerative and Neuroinflammatory Disease

Astrocytes and microglia change their behavior in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, infections, epilepsy, stroke, and traumatic injury.

These responses may be protective in some phases and harmful in others. Observing activated glia in diseased tissue does not by itself prove that glia caused the disease.

Common Misunderstandings

“Glial cells are just glue.”

The term glia comes from a word meaning glue, but glial cells do much more than provide structural support. They regulate signaling, metabolism, myelin, immune responses, development, and tissue repair.

“The brain has ten times more glial cells than neurons.”

This is an outdated generalization. Total numbers are roughly comparable across the whole human brain, and the ratio differs substantially among brain regions.[1]

“Glial cells do not communicate.”

Glial cells communicate with neurons and other glia using chemical, electrical, metabolic, and contact-dependent signals. Most do not use long axons and rapid action potentials in the same way as neurons.

“All glial cells have the same origin.”

Most astrocytes, oligodendrocytes, and ependymal cells arise from neural lineage cells. Microglia arise from an early myeloid lineage associated with the embryonic yolk sac.[2]

“All glial activation damages the brain.”

Glial responses can protect tissue, clear debris, contain injury, and support repair. Under other conditions, persistent or dysregulated responses may contribute to inflammation and tissue damage.

“Myelin is formed by only one type of cell.”

Oligodendrocytes form myelin in the CNS, while Schwann cells form myelin in the PNS.

Glial cells are essential non-neuronal cells of the nervous system.
Astrocytes regulate the environment around neurons, synapses, and blood vessels.
Oligodendrocytes form myelin in the brain and spinal cord.
Microglia are resident immune cells with a distinct embryonic origin.
Ependymal cells line the ventricles and central canal.
Schwann cells myelinate and support peripheral axons.
Satellite glial cells surround neurons in peripheral ganglia.
Glia actively communicate with neurons and influence neural development and function.
The frequently repeated 10:1 glia-to-neuron ratio is not accurate for the entire human brain.

References

von Bartheld CS, Bahney J, Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. Journal of Comparative Neurology. 2016;524(18):3865–3895. doi:10.1002/cne.24040. PubMed
Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–845. doi:10.1126/science.1194637. PubMed
Allen NJ, Lyons DA. Glia as architects of central nervous system formation and function. Science. 2018;362(6411):181–185. doi:10.1126/science.aat0473. PubMed Central
Fields RD, Stevens-Graham B. New insights into neuron-glia communication. Science. 2002;298(5593):556–562. doi:10.1126/science.298.5593.556. PubMed

Brain Basics Article INDEX

Written by: MedMaru Editorial Team
Reviewed for medical accuracy by: S. Chang, KMD