Schwann cells are specialized support cells and the primary glial cells of the Peripheral Nervous System (PNS). The PNS includes all nerves outside the brain and spinal cord. Derived from the neural crest during embryonic development, these cells are essential for the health and function of motor and sensory neurons. They surround and protect the long, slender projections of nerve cells known as axons.
Schwann cells provide the necessary structural and metabolic support to peripheral axons, ensuring they can transmit electrical signals efficiently over long distances. This protective presence is necessary for the peripheral nervous system to coordinate the body’s movements and sensations.
Insulating the Axon Myelin Sheath Formation
The most recognized function of Schwann cells is forming the myelin sheath, a thick, lipid-rich layer that wraps around the axons of larger peripheral nerves. A single myelinating Schwann cell tightly coils its plasma membrane around a single large-diameter axon. This concentric wrapping creates dense, multi-layered insulation, rich in lipids and proteins, which dramatically changes how the electrical nerve impulse travels.
The myelin sheath is segmented, with small gaps remaining between adjacent Schwann cells called the Nodes of Ranvier. At these nodes, the axonal membrane is exposed to the extracellular environment. The nodes contain a high concentration of voltage-gated sodium channels.
This segmented structure allows for saltatory conduction, meaning the impulse “leaps” or “jumps” rapidly from one Node of Ranvier to the next. This mechanism increases the speed of nerve impulse transmission by up to 100 times compared to unmyelinated axons.
Not all peripheral axons are myelinated; Schwann cells also have a non-myelinating role for smaller nerve fibers. Non-myelinating Schwann cells may ensheath several small-diameter axons simultaneously. These groups of unmyelinated fibers bundled within a single Schwann cell are referred to as Remak bundles.
Essential Maintenance and Support Functions
Beyond insulation, Schwann cells are actively involved in the maintenance and survival of the peripheral neurons they surround. They provide continuous trophic support, delivering necessary nutrients and growth factors to the axon. This supportive role is important for the distal segments of long peripheral axons, which are far from the neuron’s cell body.
The cells secrete neurotrophic factors, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), that promote axonal health and regulate metabolism. They also shuttle energy metabolites, such as lactate, to the axon through specialized transporters. This metabolic partnership ensures the long-term viability of the peripheral nerve fiber.
Schwann cells also maintain the structural integrity of the nerve by contributing to the extracellular matrix. They deposit and organize the basal lamina, a thin layer of specialized extracellular material that surrounds each cell. This scaffold provides physical support and a signaling environment that helps regulate interactions between the axon and its surrounding glial cell.
Non-myelinating Schwann cells, which form the Remak bundles, provide a protective cushioning effect to the smaller, slower-conducting axons they enclose. By enveloping these fibers, they help shield them from mechanical stresses and fluctuations in the local environment. This structural support is important for the function of these pain and temperature-sensing fibers.
The Role in Nerve Regeneration After Injury
Schwann cells actively participate in the regeneration of peripheral nerves following injury, a capacity largely absent in the Central Nervous System (CNS). When a peripheral nerve is severed or crushed, the distal segment of the axon immediately undergoes Wallerian degeneration. During this process, the axon and its myelin sheath rapidly break down and disintegrate.
Schwann cells quickly transition from their mature, insulating state to a highly active, proliferative repair state. They begin to clear cellular debris, including the remnants of the axon and broken-down myelin. This cleanup is necessary because myelin debris contains inhibitory molecules that would otherwise block nerve regrowth.
Debris clearance involves phagocytosis, where Schwann cells engulf external fragments, and myelinophagy, where they digest the myelin internally. The removal of this inhibitory material prepares the environment for the injured axon to regrow. The activated repair Schwann cells then align themselves within the basal lamina tubes, forming structures known as the Bands of Büngner.
The Bands of Büngner act as an organized scaffold, forming a guidance track for regenerating axon sprouts. The Schwann cells within these bands secrete a high concentration of neurotrophic factors and cell adhesion molecules, creating a chemically attractive pathway. These molecular cues direct the advancing tip of the injured axon, or growth cone, back toward its original target.
If the physical scaffold of the nerve sheath remains intact, the regenerating axon has a high chance of navigating to its correct destination, leading to functional recovery. This organized, multi-step process, orchestrated by Schwann cells, explains why peripheral nerve injuries often recover, while similar damage in the brain or spinal cord typically results in permanent loss of function.
When Schwann Cells Malfunction
When Schwann cells fail to perform their duties due to genetic defect, autoimmune attack, or metabolic stress, the result is a range of debilitating peripheral neuropathies. A failure in myelinating function leads to a loss of the insulating sheath, which severely reduces the speed and efficiency of nerve conduction. This demyelination can cause symptoms such as muscle weakness, numbness, and difficulty with balance.
In Guillain-Barré Syndrome (GBS), the immune system mistakenly attacks the myelin sheaths produced by Schwann cells, causing rapid-onset muscle weakness and paralysis. The destruction of the myelin disrupts signal transmission, often leading to a medical emergency.
Another class of disorders, such as Charcot-Marie-Tooth (CMT) disease, involves inherited genetic mutations that directly affect Schwann cell structure or function. These mutations cause either improper formation (dysmyelination) or slow, progressive breakdown (demyelination) of the myelin sheath. CMT is characterized by slow nerve conduction velocities and a gradual loss of sensation and muscle control, particularly in the feet and hands.
Metabolic conditions like diabetes mellitus can also severely damage Schwann cells, leading to diabetic peripheral neuropathy. High blood sugar levels (hyperglycemia) impair the cell’s function, causing a loss of trophic support to the axons. This results in the nerves dying back, often beginning in the longest nerves that reach the feet, leading to pain, numbness, and eventual loss of protective sensation.