What Are Glial Cells?

Glial cells — also called glia or neuroglia — are non-neuronal cells found throughout the central nervous system and peripheral nervous system. They physically and metabolically support neurons: insulating them, helping them communicate, and moving nutrients and waste in and out.

Glia is an umbrella term for several distinct cell types, including microglia, astrocytes, and Schwann cells. Each type does its own job. Together, they keep the brain functioning.

Primarily, glial cells provide support and protection to the neurons (nerve cells), maintain homeostasis, clean up debris, and form myelin. They essentially work to care for the neurons and the environment they are in.

Glia are popularly said to outnumber neurons about ten to one. That figure is outdated. Careful whole-brain counts put the two cell types at close to parity instead (Azevedo et al., 2009).

A 150-year review of cell-counting methods agrees. It found no solid evidence for the old ratio (von Bartheld et al., 2016).

For most of the twentieth century, glia were assumed to be purely structural “nerve glue.” That view has changed. Glia are now known to actively shape synapses and contribute to learning, memory, and mood (Fields & Stevens-Graham, 2002).

What do glial cells do?

Glial cells perform many behind-the-scenes jobs that are essential to brain and nerve health:

• Support neurons physically and metabolically
• Insulate axons with myelin to speed up signals
• Maintain homeostasis in the brain’s internal environment
• Clear debris and dead cells
• Regulate neurotransmitter levels
• Assist in immune defense within the brain
• Guide brain development and support plasticity

Together, these tasks help neurons fire, recover, and stay healthy throughout life.

Think of Glial Cells Like a Support Crew

Astrocytes = Janitors + Supply Managers
They clean up debris, mop up excess chemicals, regulate nutrients, and even store energy—keeping neurons in top shape.

Microglia = Immune Patrols
They’re the brain’s defense squad, constantly scanning for threats, cleaning up damage, and helping with repairs.

Oligodendrocytes / Schwann Cells = Electricians
These cells insulate neuronal wiring (axons) with myelin, ensuring fast, efficient signal transmission.

Glial cells vs neurons

Glial cells differ from neurons in terms of structure. Neurons will have an axon and dendrites to transfer electrical signals between other nerve cells.

Glial cells, however, do not have axons or dendrites.

This means that glial cells do not participate directly in synaptic interactions and electrical signaling, although they are supportive in helping the neurons maintain these functions.

Also, although glial cells have complex extensions from their cell bodies since they do not have axons or dendrites, this makes them typically smaller than neurons.

Astrocytes, which are the largest type of glial cell, have a diameter of 40-50 microns.

Glial cells in the central nervous system (CNS)

Microglia

Microglia are the brain’s resident immune cells, constantly monitoring tissue for injury, infection, or unusual activity.

After injury, they migrate to the damage. They engulf dead cells and debris, and help create the conditions for repair.

Microglia also prune synapses. During development, and to a lesser extent in adulthood, they physically remove weak or surplus synaptic connections, refining neural circuits, especially during adolescence.

The same molecular tagging system behind this pruning appears to be reactivated early in Alzheimer’s disease (see Contemporary Research, below).

Microglia sit at the intersection of immune function and synaptic remodelling. Their dysfunction connects surprisingly different conditions.

It has been linked to chronic pain and fibromyalgia (Ohgidani et al., 2017), and to atypical developmental pruning in autism (Tetreault et al., 2012).

Astrocytes

Astrocytes — star-shaped cells named from the Greek for “star” — maintain the neuronal environment. They regulate neurotransmitters, recycle glutamate, clear debris, remove excess potassium, help form the blood-brain barrier, and store energy for neurons.

Astrocyte processes physically wrap around synapses. Araque et al. (1999) proposed this makes the astrocyte an active third partner in the “tripartite synapse.”

It senses nearby activity and releases signalling molecules that can strengthen or weaken transmission. That is a concrete mechanism for how glia reshape neural circuits.

Astrocytes aren’t functionally uniform, though. Liddelow et al. (2017) found that activated microglia can push astrocytes into a harmful “reactive” state that promotes neuron and oligodendrocyte death, rather than supporting them.

Astrocyte dysfunction has since been linked to major neurodegenerative diseases, including ALS, Alzheimer’s, Parkinson’s, and Huntington’s disease (Phatnani & Maniatis, 2015).

The reactive state can potentially be reversed. Blocking the signal that triggers it is being explored as a neuroprotective treatment strategy.

Oligodendrocytes

Oligodendrocytes are the CNS’s myelinating glia. Each one wraps segments of several different axons in fatty, insulating myelin sheaths.

That dramatically speeds up electrical signal conduction, and also provides nutrients to the axon.

This differs from the peripheral nervous system’s Schwann cells, which each myelinate only one segment of one axon.

The difference matters clinically. That structural difference is one reason central and peripheral nerve diseases can look clinically different.

Oligodendrocyte and myelin problems are linked to multiple sclerosis and leukodystrophies. They matter for psychiatry too. Brain-imaging studies have found myelination deficits in schizophrenia (Scheel et al., 2013).

Later work proposes oligodendrocyte abnormalities as a contributing mechanism in schizophrenia and mood disorders, not just a downstream effect of illness (Schmitt et al., 2019).

A related line of evidence draws a direct parallel between oligodendrocyte abnormalities in bipolar disorder and the oligodendrocyte pathology of multiple sclerosis (Konradi et al., 2012).

Ependymal cells

Ependymal cells line brain ventricles and the spinal cord’s central canal, circulating and producing cerebrospinal fluid.

Their dysfunction is associated with hydrocephalus (Ji et al., 2022), multiple sclerosis (Hatrock et al., 2020), and may contribute to neurodegenerative diseases (Nelles & Hazrati, 2023).

Radial glial

Radial glia are elongated cells spanning the developing brain, from where new neurons are born to the cortex’s outer surface.

Rakic (1972) showed that new neurons migrate outward along these fibres like climbers on a rope, using them as a scaffold to reach the right cortical layer.

Radial glia aren’t just passive scaffolding, though. Noctor et al. (2001) found that many cortical neurons are themselves direct offspring of radial glia, overturning the old assumption that neurons and radial glia were separate lineages.

A subset persists into adulthood. These cells act as neural stem cells, generating new neurons and glia throughout life (Alvarez-Buylla et al., 2001).

That is one reason radial glia are of interest in research on repairing brain damage and brain plasticity.

A Second Look at Glial Cells

For years, glial cells were dismissed as “nerve glue” with little purpose. Today, we know they’re active participants in brain health—regulating mood, inflammation, development, and even memory. They’re not just support; they’re essential.

Glial cells in the peripheral nervous system (PNS)

Schwann cells

Schwann cells provide myelin insulation for peripheral nervous system axons and aid in nerve regeneration.

Abnormalities can lead to conditions like Guillain-Barre syndrome and Charcot-Marie-Tooth disease. Their dysfunction may trigger harmful inflammation in neuropathies (Ydens et al., 2013).

Satellite cells

Satellite cells surround nerve cell bodies in ganglia, regulating the neuronal environment and providing protection.

Their dysfunction may affect sensory processes and organ communication. Satellite cell issues are linked to muscle disorders (Servián-Morilla et al., 2020; Ganassi et al., 2022).

Spindle Cells (Von Economo Neurons)

Alongside the glial cells above, the anterior cingulate cortex (ACC) contains an unusual neuron. This region is involved in emotion and social cognition. Spindle cells, more formally von Economo neurons, are large and spindle-shaped.

They occur almost nowhere else. Unlike the cells covered above, spindle cells are neurons, not glia.

They are grouped here because both are frequently discussed as recent refinements to the standard picture of the brain. Glial and spindle-cell disease also turn out to overlap, as the studies below show.

Spindle cells occur in humans and great apes.

They are common in humans and chimpanzees, sparser in gorillas and orangutans. They are absent from every other species studied (Nimchinsky et al., 1999).

Why does that matter? This lineage is also marked by complex social cognition. Spindle cells have been proposed as part of the neural basis for fast, intuitive social-emotional judgement (Allman et al., 2005).

Discovery: Nimchinsky et al. (1999)

A simple question drove this study. Were the odd, spindle-shaped neurons occasionally seen in the human anterior cingulate cortex a genuinely distinct type?

Aim: To determine that, and to find out which other species also carry them.

Method: Post-mortem staining. The researchers compared anterior cingulate tissue across many species: humans, chimpanzees, gorillas, orangutans, and several monkey and other mammal species.

Findings: A large, spindle-shaped neuron turned up consistently in humans and great apes, most in humans and chimpanzees. It was absent everywhere else.

Conclusion: This is an evolutionarily recent cell type, confined to the great-ape/human lineage. That motivated a new hypothesis: perhaps it supports social-cognitive processing.

Evaluation: This is a careful, systematic study, and its core finding has been widely replicated.

Its main limit is that it is purely descriptive. What the cells actually do remains an inference, not a direct test.

Spindle Cells and Disease: Seeley et al. (2006)

Does that hypothesis hold up in disease? Seeley and colleagues put it to the test.

Aim: To test whether spindle cells are selectively lost in frontotemporal dementia (FTD), a condition marked by early social and behavioural change, and whether that loss is specific to FTD.

Method: Unbiased stereological cell-counting. The researchers compared anterior cingulate spindle cells and neighbouring neurons in post-mortem tissue from people with FTD, Alzheimer’s disease, and non-demented controls (n = 5-7 per group).

Findings: FTD patients showed severe, selective spindle-cell loss, a 74% reduction versus controls. This was independent of general neuronal loss.

Alzheimer’s disease patients, by contrast, showed essentially normal spindle-cell counts and structure, despite substantial local tangle pathology.

Conclusion: Spindle-cell loss is a relatively selective marker of FTD, not of dementia in general.

This ties FTD’s early social symptoms to damage in exactly the neuron population hypothesised to support social-emotional intuition.

Evaluation: Stereology helps here. So does including both a disease-control group and a healthy-control group, which strengthens the disease-specificity claim.

The main limitation is sample size. Five to seven cases per group is typical for post-mortem work, but modest.

FAQs

Critical Evaluation

Glial and spindle-cell research has genuinely changed how neuroscience understands the brain. But some claims are better supported than others. The sections below weigh the newest evidence and flag which popular claims go too far.

Contemporary Research

Two recent, high-impact findings update the picture.

Spindle Cells and Alzheimer’s Disease

Spindle cells are dramatically lost in FTD. But they are largely spared in Alzheimer’s disease (Seeley et al., 2006). Gefen et al. (2018) tested that directly.

Aim: To see how spindle-cell density changes with normal ageing, exceptional old-age cognitive preservation (“SuperAgers”), and across the stages of Alzheimer’s disease.

Method: Stereological counts. Researchers measured anterior cingulate spindle cells and total neurons in post-mortem tissue from five small groups (n = 5 each). The groups: younger controls, SuperAgers, older controls, mild cognitive impairment, and Alzheimer’s disease.

Findings: Density stayed stable across normal ageing. SuperAgers had the highest density of any group.

Alzheimer’s disease patients had significantly lower density than controls, and density fell as Braak stage, a measure of tangle severity, rose.

Conclusion: Spindle cells are genuinely vulnerable to Alzheimer’s pathology. But the loss tracks disease severity gradually, unlike FTD’s early, dramatic loss.

Preserved spindle-cell density may be one marker of exceptional cognitive resilience in old age.

Microglia and Early Synapse Loss in Alzheimer’s Disease

Synapse loss is one of the earliest signs of Alzheimer’s disease. Why does it begin before amyloid plaques appear?

Hong et al. (2016) went looking for an answer.

Published in Science, the study tested whether the same complement-and-microglia pathway that prunes synapses in healthy brain development is abnormally switched back on.

Aim: To find out. Specifically, to determine whether complement proteins and microglia drive early, pre-plaque synapse loss in mouse models of Alzheimer’s disease.

Method: Researchers tracked the complement protein C1q at synapses in genetically modified Alzheimer’s-model mice. They then tested causality by deleting the downstream complement protein C3, and by blocking microglial engulfment.

Findings: C1q built up at synapses well before plaques formed. Deleting C3 substantially reduced early synapse loss.

That directly implicates the complement cascade, acting through microglia.

Conclusion: The same “trash disposal” pruning system that sculpts healthy circuits during development appears to switch back on early in Alzheimer’s disease.

It drives synapse loss before the disease’s more familiar hallmarks appear.

How Strong Is the Evidence?

Much of the disease evidence above comes from post-mortem or cross-sectional comparisons. These can’t, on their own, separate a causal contribution to the disorder from a downstream consequence of it.

The Hong et al. (2016) mouse study is a partial exception. It manipulates the mechanism directly, rather than only observing it.

Some popular claims go further than the evidence. Take the idea that unusually dense glia explain individual genius, often linked to comparisons of Einstein’s preserved brain tissue.

That rests on isolated case comparisons, not a systematic, well-replicated evidence base. It is better treated as folklore than an established finding.

Similarly, “spindle cells make us human” overstates the evidence. Their presence really is restricted to humans and great apes (Nimchinsky et al., 1999).

Disease-specific vulnerability is real too (Seeley et al., 2006). But no study links spindle-cell density to any single human trait.

This is a hypothesis, not a demonstrated fact.

References

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Hatrock, D., Caporicci-Dinucci, N., & Stratton, J. A. (2020). Ependymal cells and multiple sclerosis: proposing a relationship. Neural regeneration research, 15(2), 263.

Jäkel, S., & Dimou, L. (2017). Glial cells and their function in the adult brain: a journey through the history of their ablation. Frontiers in cellular neuroscience, 11, 24.

Ji, W., Tang, Z., Chen, Y., Wang, C., Tan, C., Liao, J., … & Xiao, G. (2022). Ependymal cilia: Physiology and role in hydrocephalus. Frontiers in Molecular Neuroscience, 15, 927479.

Konradi, C., Sillivan, S. E., & Clay, H. B. (2012). Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis. Neurobiology of disease, 45(1), 37-47.

Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., … & Barres, B. A. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541(7638), 481-487.

Nelles, D. G., & Hazrati, L. N. (2023). The pathological potential of ependymal cells in mild traumatic brain injury. Frontiers in Cellular Neuroscience, 17, 1216420.

Ohgidani, M., Kato, T. A., Hosoi, M., Tsuda, M., Hayakawa, K., Hayaki, C., … & Kanba, S. (2017). Fibromyalgia and microglial TNF-α: translational research using human blood induced microglia-like cells. Scientific reports, 7(1), 11882.

Phatnani, H., & Maniatis, T. (2015). Astrocytes in neurodegenerative disease. Cold Spring Harbor perspectives in biology, 7(6), a020628.

Purves, D. A. GJ., Fitzpatrick, D., et al. (2001). Neuroscience 2nd edition. Neuroglial cells.

Scheel, M., Prokscha, T., Bayerl, M., Gallinat, J., & Montag, C. (2013). Myelination deficits in schizophrenia: evidence from diffusion tensor imaging. Brain Structure and Function, 218, 151-156.

Servián-Morilla, E., Cabrera-Serrano, M., Johnson, K., Pandey, A., Ito, A., Rivas, E., … & Paradas, C. (2020). POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern. Acta neuropathologica, 139, 565-582.

Schmitt, A., Simons, M., Cantuti-Castelvetri, L., & Falkai, P. (2019). A new role for oligodendrocytes and myelination in schizophrenia and affective disorders?. European Archives of Psychiatry and Clinical Neuroscience, 269, 371-372.

Tetreault, N. A., Hakeem, A. Y., Jiang, S., Williams, B. A., Allman, E., Wold, B. J., & Allman, J. M. (2012). Microglia in the cerebral cortex in autism. Journal of Autism and Developmental Disorders, 42(12), 2569-2584.

Ydens, E., Lornet, G., Smits, V., Goethals, S., Timmerman, V., & Janssens, S. (2013). The neuroinflammatory role of Schwann cells in disease. Neurobiology of disease, 55, 95-103.