Glial cells – a short summary
In the central nervous system (CNS) and the peripheral nervous system (PNS), we find non-neuronal cells known as glia or glial cells. The term „glia“ was first coined by the German anatomist Rudolf Virchow in 1856, who believed these cells acted as „glue“ to hold the nervous system together. However, it wasn’t until the 20th century that the true complexity and diverse functions of glial cells were revealed. Today, we know that glia play essential roles beyond structural support, including modulating neuronal activity, maintaining homeostasis, facilitating information processing in the brain, and protecting neurons from injury.
Glial cells are smaller than neurons but are equal in number to neurons in the human brain (approximately 85 billion glial cells). The glia-to-neuron ratio varies depending on the brain region. In the CNS, glial cells include astrocytes, oligodendrocytes, microglia, ependymal cells, tanycytes, and radial glia (including Bergmann glia in the cerebellum and radial MĂĽller cells in the retina). In the PNS, glial cells include Schwann cells, satellite cells, and enteric glial cells.
Astrocytes
Astrocytes, named after the ancient Greek word astron, meaning „star,“ have a characteristic star-shaped structure. These cells were first described in the 19th century by the German neurologist Rudolf Virchow. One of their major roles is the formation of the blood-brain barrier (BBB), achieved by encircling endothelial cells with their endfeets, thus regulating the passage of substances between the bloodstream and the CNS. Astrocytes control the exchange of ions, nutrients, and metabolic waste, which is crucial for maintaining the brain’s homeostasis. They also regulate the uptake and recycling of neurotransmitters, particularly glutamate, preventing excitotoxicity, which could lead to neuronal damage.
Astrocytes are involved in neurovascular coupling, which is the process where blood flow is increased to brain areas that are more actively engaged in neuronal activity. This helps ensure that active neurons receive an adequate supply of oxygen and nutrients.
They are also capable of releasing gliotransmitters such as ATP, glutamate and D-serine, which influence synaptic plasticity and neuronal communication. This has led to the understanding of the „tripartite synapse,“ where astrocytes, in addition to pre- and post-synaptic neurons, actively participate in synaptic function.
Astrocytes also play a role in neuroinflammation by releasing cytokines in response to injury or disease, contributing to the regulation of the immune response within the brain.
In the event of neuronal injury, astrocytes undergo astrogliosis and form a glial scar. While this repair process is beneficial for limiting damage, prolonged or excessive astrogliosis can impair neuronal regeneration and synaptic plasticity.
Oligodendrocytes
Oligodendrocytes (OLs) were discovered by the Spanish pathologist PĂo del RĂo Hortega in 1928. Their name, derived from the Greek words oligo (few) and dendron (tree), reflects their few, branching processes. Oligodendrocytes arise from oligodendrocyte precursor cells (OPCs) and are responsible for myelinating axons in the CNS. The myelin sheath is essential for insulating axons and enabling saltatory conduction, where the action potential jumps between nodes of Ranvier, speeding up the transmission of action potential. Myelination is crucial for efficient communication between neurons.
Moreover, oligodendrocytes provide metabolic support to axons by shuttling lactate and glucose, which are vital for axonal function, and producing trophic factors that promote neuronal survival and growth.
It has also been shown that oligodendrocytes are involved in the regulation of the immune system by secreting cytokines and chemokines in response to injury or disease, which helps modulate the immune response in the brain. Recent studies suggest that oligodendrocytes play a role in synaptic plasticity, not just in myelination. They interact with neurons to modulate synapse formation and pruning, which is critical for learning and memory. In diseases like multiple sclerosis (MS), the immune system mistakenly attacks oligodendrocytes, leading to demyelination, which disrupts neuronal communication and results in motor, sensory, and cognitive deficits.
Microglia
Microglia, discovered by the Spanish anatomist Santiago RamĂłn y Cajal in the early 20th century, are the primary immune cells of the CNS. They function as the brain’s first line of defense, constantly monitoring for pathogens, damaged neurons and other disruptions in brain homeostasis. In their resting state, microglia have a ramified, highly branched morphology that allows them to survey large areas of the brain tissue. Upon detecting pathogens or neural injury, microglia transition to a reactive form where they retract their branches, become amoeboid, and begin phagocytosis of foreign materials, dead cells, and debris. They also release cytokines and chemokines to activate the broader immune response. They also play a significant role in synaptic pruning during development and plasticity, eliminating unnecessary or weak synapses to refine neuronal circuits. This process is important for learning, memory and brain development. Dys-regulated microglial activity has been implicated in various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and neurodevelopmental disorders like autism spectrum disorder (ASD), where excessive or inadequate pruning can contribute to pathology.
Ependymal Cells
Ependymal cells line the ventricles of the brain and the central canal of the spinal cord, forming a barrier between the cerebrospinal fluid (CSF) and the neural tissue. These cells play a crucial role in the production and regulation of CSF, which cushions the brain and removes metabolic waste. Ependymal cells have a ciliated surface, and in some regions, these cilia help circulate CSF throughout the ventricular system.
They also contribute to neurogenesis by maintaining a pool of neural stem cells in the adult brain, particularly in the subventricular zone. These stem cells can differentiate into neurons and glial cells. Ependymal cells also have microvilli that assist in the absorption of CSF, helping to regulate fluid balance in the brain and spinal cord. In certain conditions, such as spinal cord injury or stroke, ependymal cells can become reactive and attempt to regenerate neural tissue, although this regenerative ability is limited in the adult CNS.
Tanycytes
Tanycytes are specialized ependymal cells that have long basal processes extending from the ventricles into the hypothalamus. They play a role in the communication between the brain’s CSF and the blood-brain barrier. Tanycytes are also involved in regulating neuroendocrine functions, such as the secretion of hormones from the hypothalamus, which control various metabolic processes like hunger, thirst, and stress. They have been found to play a role in the regulation of energy balance and circadian rhythms, especially through their interactions with the hypothalamus, which governs hunger, sleep, and temperature regulation.
Radial Glia
Radial glial cells are bipolarly shaped progenitor cells that originate from neuroepithelial cells during neurogenesis. They act as scaffolds for newly formed neurons to migrate to their proper destinations during brain development. Radial glia also differentiate into various glial cell types, including astrocytes and oligodendrocytes.
Bergmann glia, also known as radial astrocytes, are unipolar astrocytes derived from radial glia that are found in the cerebellum in close association with Purkinje cells. Because of their astrocyte-like characteristics, they are often referred to as “specialized astrocytes.” They assist in the migration of granule cells, the smallest neurons in the brain, from the external granular layer to the internal granular layer. Like astrocytes, Bergmann glia undergo extensive changes to replace damaged tissue following CNS injury, a process known as gliosis. They also contribute to synaptic pruning.
MĂĽller glia, a type of radial glia found in the retina, possess long processes that span the entire width of the retina. These cells have unique optical properties, distinguishing them from other radial glia in the CNS. MĂĽller glia act as the main fiber that transmits light to photoreceptors in the retina. Remarkably, they perform many of the functions typically handled by astrocytes and oligodendrocytes in the CNS.
Schwann Cells
Schwann cells, named after the German physiologist Theodor Schwann, are the principal glial cells of the PNS. There are two types of Schwann cells: myelinating and non-myelinating (named also Remak Schwann cells). Myelinating Schwann cells form a myelin sheath around motor and sensory axons that extend from the spinal cord to muscles or other organs. Each myelinating Schwann cell myelinates only one axonal segment. These cells are analogous to oligodendrocytes in the CNS, providing insulation for axons and enabling saltatory conduction. They also provide trophic support for neurons.
Nonmyelinating Schwann cells, on the other hand, maintain axons and are crucial for neuronal survival. They can form Remak bundles by grouping around smaller axons. Schwann cells also play a vital role in nerve regeneration. After nerve damage, they assist in axon phagocytosis and form a tunnel that guides regenerating axons, allowing them to reconnect with their target muscle or organs. Thus, Schwann cells are essential for maintaining healthy axons and ensuring the transmission of information from the CNS to the rest of the body.
Satellite Cells
Satellite glial cells (SGCs) surround the cell bodies of neurons in the sensory, sympathetic, and parasympathetic ganglia. They play roles in nutrient supply, waste removal, and electrochemical regulation within the ganglionic environment.
SGCs can modulate neuronal activity in response to physiological or pathological stimuli, including pain, stress, and inflammation. They are involved in maintaining the homeostasis of the extracellular environment, particularly by controlling ion concentrations. SGCs also participate in the response to injury in the PNS and can support axonal regeneration by secreting neurotrophic factors.
Enteric Glial Cells
Enteric glial cells (EGCs) are located in the gastrointestinal tract and play crucial roles in regulating the gut-brain axis, modulating both local gastrointestinal function and central nervous system activity. EGCs maintain intestinal homeostasis by supporting enteric neurons, regulating immune responses, and managing gut motility.
EGCs regulate intestinal inflammation and the immune response in the gut. They respond to injury and infection by secreting cytokines and chemokines to control local immune responses and neuronal function. Research has shown that EGCs play a role in modulating pain perception in the gut, potentially contributing to conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
a contribution by Tala Karam (Sorbonne Université, Paris, France)