TLL 16x Glial Cells

Glial Cells

Glial cells are non-neuronal cells in the nervous system that support, protect, and nourish neurons. They outnumber neurons but it varies by region.

There are four types of glial cells with descriptive names in the central nervous system (CNS):

• Astrocytes - provide structural and metabolic support for neurons
• Oligodendrocytes - form myelin sheaths around axons
• Microglia - resident immune cells that resemble macrophages
• Ependymal Cells - line the ventricles of the brain and central canal of the spinal cord

We will take a closer look at these cells in the following pages.

Subcellular Structures

• Nucleus (blue) / Nucleolus (yellow) / Nuclear Envelope (purple)
• Golgi Apparatus (yellow)
• Mitochondria (red)
• Endoplasmic Reticulum (cyan)
• Lysosomes (orange)
• Cytoskeleton - intermediate filaments (blue) and microtubules (cyan)

Courtesy of Thomas L. Lentz, Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut.

Astrocytes

Astrocytes provide structural and metabolic support to neurons, maintain the concentrations of ions and chemicals in the extracellular fluid, and remove neurotransmitters.

• Stellate Shape - many processes radiating outwards from the cell body
• Cell Body - large nucleus with dispersed chromatin and cytoplasm rich in organelles
  • Size and shape vary depending on subtype
• Processes - complexity and length of processes vary between astrocyte subtypes
• Endfeet - specialized structures at the tips of many astrocyte processes
  • Perivascular Endfeet - completely cover blood vessels, contributing to the blood-brain barrier
  • Glia Limitans - endfeet cover the outer surface of the brain and spinal cord, creating a barrier between cerebrospinal fluid and the brain
• Cytoskeleton - abundant intermediate filaments of Glial Fibrillary Acidic Protein (GFAP)
  • GFAP is a key diagnostic marker for astrocytes

There are two major subtypes: protoplasmic astrocytes and fibrous astrocytes. Other less common subtypes have been identified based on their unique structure or gene expression, usually with restricted distribution.

Protoplasmic Astrocytes

Protoplasmic astrocytes provide structural and metabolic support to neurons. They maintain concentrations of ions and chemicals in the extracellular fluid, remove neurotransmitters, and release molecules that influence the activity of nearby synapses.

They are stellate cells with many highly branched processes, found primarily in gray matter (regions rich in neuronal cell bodies, dendrites, and synapses).

• Cell body - large nucleus (blue) with dispersed chromatin and cytoplasm rich in organelles
• Processes - numerous highly branched processes that interact with elements in the nearby neuropil
  • Encapsulate axon terminals (orange) and dendritic spines (light blue)
  • Contact neuronal cell bodies and dendrites (dark green)
  • Fill empty spaces between axons (yellow)
• Perivascular Endfeet - specialized structures at the tips of many processes that cover blood vessels, contributing to the blood-brain barrier
• Cytoskeleton - tight bundles of intermediate filaments of Glial Fibrillary Acidic Protein (GFAP)
• Glycogen Granules - store large amounts of glucose as an energy reserve for neurons during times of high synaptic activity
• Gap Junctions - interconnect neighboring astrocytes, creating functional networks enabling coordinated activity, rapid communication, or distribution of nutrients or buffering ions

Protoplasmic astrocytes occupy distinct spatial domains with minimal overlap between adjacent cells.

Fibrous Astrocytes

Fibrous Astrocytes provide structural support and help maintain the integrity of nerve tracts. They help maintain the myelin sheath by interacting with oligodendrocytes and ensuring the proper environment for these cells.

They are stellate cells with fewer long, less branched processes, found mainly in white matter (regions rich in myelinated axons).

• Cell body - large nucleus (blue) with dispersed chromatin and cytoplasm with fewer organelles
• Processes - fewer large processes that branch into long, thin processes that align with myelinated fibers in white matter
• Perivascular Endfeet - specialized structures at the tips of many processes that cover blood vessels, contributing to the blood-brain barrier
• Cytoskeleton - most noticeable feature is the numerous intermediate filaments of Glial Fibrillary Acidic Protein (GFAP) in the cell body and processes
  • Filaments more dispersed than the tight bundles of protoplasmic astrocytes
  • Provide rigidity to the long, thin processes

Oligodendrocytes

Oligodendrocytes support nerve fibers and produce myelin sheaths, which provide electrical insulation and speed up nerve impulse transmission. These cells are found mainly in the white matter (regions rich in myelinated fibers) of the central nervous system.

To simplify their complex architecture, this drawing illustrates the cell body myelinating only a single segment of an axon.

• Cell Body - small nucleus (blue) of condensed chromatin and cytoplasm rich in organelles
  • Multiple well-developed Golgi apparatus (yellow)
  • Abundance of protein and lipid synthesis machinery to produce large amounts of myelin membrane
  • Store small amounts of glycogen
• Processes - extend processes that reach out to as many as 50 axons
  • Each process forms one segment of the myelin sheath around an axon
  • Myelin Sheath - tightly compacted, concentric layers (lamellae) of the oligodendrocyte's cell membrane
• Cytoskeleton - many microtubules but lack intermediate filaments
  • During the early stages of development, the intermediate filament vimentin is expressed, but it is lost during maturation.
• Do not accumulate lipid inclusions during aging and disease

Microglia

Microglia are resident immune cells in the central nervous system. They engulf and digest dead cells, cellular debris, and pathogens, similar to macrophages in the rest of the body.

They are the smallest and least numerous of the glial cells, frequently found near blood vessels and neuronal cell bodies.

• Cell Body - small nucleus (blue) of condensed chromatin and little cytoplasm
  • Distinctive long cisternae of rough endoplasmic reticulum (cyan), contrary to other glial cell types
  • Many lysosomes (orange), lipofuscin (black), and other lipid bodies
• Processes - extend long, thin processes with irregular contours
  • Highly dynamic, rapidly extending and retracting to survey their environment
• Cytoskeleton - significantly fewer filaments compared to other glial cell types
  • Dynamic rearrangement of actin filaments is crucial for motility and phagocytosis

When microglia detect a problem, they undergo a process known as “activation.” The cell body enlarges as processes retract to allow movement toward areas of injury, inflammation, or infection. The activated microglia become phagocytic clearing away cellular debris or foreign substances.

Ependymal Cells

Ependymal Cells line the ventricles of the brain and the central canal of the spinal cord. They play a crucial role in the production and circulation of cerebrospinal fluid (CSF), which cushions the brain and spinal cord, provides nutrients, and removes waste.

• Single layer of cuboidal to columnar cells
• Large, round nucleus (blue) and numerous mitochondria (red)
• Apical surface faces the cerebrospinal fluid
  • Cilia - axoneme of microtubules (red) anchored to basal bodies
    • Beat rhythmically to help circulate cerebral spinal fluid
  • Microvilli increase the surface area for absorption
• Lateral surfaces of adjacent cells are joined by junctional complexes (tight and adherens junctions)
• Basal surface covered by the endfeet of astrocytes
• Cytoskeleton - intermediate filaments of vimentin
  • During development also expresses Glial Fibrillary Acidic Protein (GFAP), but it is lost during maturation

Specialized ependymal cells form the choroid plexus, which is responsible for producing cerebral spinal fluid. These cells are rich in mitochondria to support their secretory function.