case 2 - glial cells

Question 1

astrocytes

Answer 1

• Astrocytes are a type of glial cell in the central nervous system (CNS) that play several important functions in supporting the overall health and function of neurons (nerve cells). Do a bit of everything
• These star-shaped cells have numerous processes that extend in various directions, allowing them to interact with neurons, blood vessels, and other components of the CNS.
• Protoplasmic (grey) and fibrillary (white)

Question 2

astrocyte key functions

Answer 2

nutrient and metabolite support (pyruvate carboxylase reaction)
ion balance (potassium-buffering)
BBB (endfeet) and bloodflow
neurotransmitter uptake/recycling (glutamate-glutamine shuttle)
neuroprotection
glial scarring
synaptic plasticity
developmental role (synaptogenesis)

Question 3

nutrient and metabolite and ion balance support

Answer 3

 Astrocytes are responsible for maintaining the optimal chemical environment for neurons.

 They help regulate the concentration of ions, such as potassium-buffer and calcium, and supply nutrients like glucose to neurons.
- Membrane potential of astrocytes (-85/90) is different (more negative) in astrocytes which is why the K goes into them and not into the neurons after action potentials

 Lactate is produced by astrocytes (can also cause inflammation when too much)
 Pyruvate carboxylase reaction: production of TCA cycle intermediates for the production of neurotransmitters

Question 4

BBB

Answer 4

 Astrocytes are involved in forming (end-feet) and maintaining the BBB, which is a selective barrier between the bloodstream and the brain tissue.
 They help regulate the passage of substances into and out of the brain, protecting it from potentially harmful agents.

Question 5

neuroprotection and glial scarring

Answer 5

 Astrocytes play a crucial role in protecting neurons from damage and oxidative stress.
 They produce antioxidants and neurotrophic factors that promote neuronal survival and growth.
 In response to injuries such as trauma or stroke, astrocytes form a glial scar.
 While this scar tissue can impede regeneration in the CNS, it also serves to contain the damage and prevent inflammation from spreading excessively.

Question 6

oligodendrocytes

Answer 6

• Oligodendrocytes are another type of glial cell found in the central nervous system (CNS), and they have several important functions related to the support and maintenance of neurons.
• Unlike astrocytes, oligodendrocytes are primarily responsible for myelination, a process where they wrap axons (the long projections of neurons) with a myelin sheath.
  o This myelin sheath acts as an insulating layer, which helps to increase the speed and efficiency of nerve signal conduction.

Question 7

oligodendrocytes functions

Answer 7

(re-)myelination
axon protection
regulation of extracellular environment (pH)

Question 8

myelination

Answer 8

o Myelination:
 The primary function of oligodendrocytes is to create and maintain the myelin sheath around axons in the CNS.
 This sheath consists of multiple layers of lipids (fats) and proteins and acts as an insulator.
 It allows nerve impulses to travel faster along the axon by reducing signal loss and energy consumption.
 Faster cause there is no leaking
 Proteins of CNS myelin debris causes growth cone collapse
* No-go protein

o Saltatory Conduction:
 Oligodendrocyte-mediated myelination enables a phenomenon known as “saltatory conduction.”
 In saltatory conduction, nerve impulses jump from one node of Ranvier (the small gaps in the myelin sheath) to another, significantly increasing the speed at which nerve signals travel along the axon.

Question 9

regulation of extracellular environment

Answer 9

 Oligodendrocytes help regulate the extracellular environment around axons by controlling the ionic composition and chemical balance of the surrounding fluid.
* pH regulation (7.4) bicarbonate buffer system (carbonic anhydrase, expressed by oligodendrocytes)
* Iron storages

Question 10

microglial cells

Answer 10

• They are the resident immune cells of the CNS and play several important functions related to immune defence, tissue maintenance, and synaptic pruning.

Question 11

microglia functions

Answer 11

immune defense
tissue maintenance
surveillance
synaptic pruning

Question 12

immune defense

Answer 12

 Microglia serve as the primary immune cells in the CNS.
 When they detect signs of infection, injury, or inflammation in the brain or spinal cord, they become activated.
 Activated microglia can phagocytose (engulf and digest) pathogens, dead cells, and cellular debris, helping to clear them from the CNS tissue.
 They also release cytokines and other signalling molecules to regulate the immune response in the brain.

o Modulation of Inflammation:
 Microglia can have both pro-inflammatory and anti-inflammatory roles.
 Depending on the signals they receive and the context, they can promote or dampen inflammation in the CNS.
 An imbalance in microglial activity can contribute to neuroinflammatory conditions.

Question 13

schwann cells

Answer 13

• Schwann cells are a type of glial cell found in the peripheral nervous system (PNS), which includes nerves outside the brain and spinal cord. These specialized cells have several important functions related to the support and maintenance of peripheral nerves, including sensory and motor neurons.

Question 14

difference in PNS and CNS myelination

Answer 14

o Location and distribution of cells:
 Schwann cells are found in the peripheral nervous system (PNS), while oligodendrocytes are located in the central nervous system (CNS).
 Schwann cells are more densely distributed since they cannot myelinate more than one axon at a time

o Myelination:
 Schwann cells myelinate a single axon each in the PNS, whereas oligodendrocytes can myelinate multiple axons in the CNS.

o Regeneration:
 Schwann cells have a crucial role in nerve regeneration in the PNS.
 They support and guide the regrowth of damaged axons. Oligodendrocytes do not play a significant role in CNS nerve regeneration, and axon regeneration in the CNS is more limited compared to the PNS. central myelin also has factors that stump the growth of growth cones of axons

o Neurological Disorders:
 Demyelinating diseases in the PNS, such as Guillain-Barré syndrome, primarily affect Schwann cells and result in peripheral nerve dysfunction.
 In the CNS, demyelinating diseases, like multiple sclerosis, involve damage to oligodendrocytes and result in CNS dysfunction.

Question 15

cellular markers - A

Answer 15

• Astrocyte Markers:
  o Glial Fibrillary Acidic Protein (GFAP): GFAP is one of the most well-known markers for astrocytes. It is an intermediate filament protein found predominantly in astrocytes and is often used to identify these cells.
   GFAP provides structural support to astrocytes and is involved in the formation of the astrocytic cytoskeleton. It helps maintain the shape and integrity of astrocytes.

o S100 Calcium-Binding Protein B (S100B): S100B is expressed in astrocytes and is used to identify and study astrocytic activity in the CNS.
 S100B is involved in calcium signalling and has various intracellular and extracellular functions, including regulating astrocyte proliferation, differentiation, and responses to injury.
 Also schwann cells (and muller cells and buglar glia)

o Glutamine synthase etc. think about exclusive functions

Question 16

markers - O

Answer 16

o Oligodendrocyte Transcription Factor 2 (OLIG2): OLIG2 is a transcription factor that plays a crucial role in the development and differentiation of oligodendrocytes. It is commonly used as a marker for these cells.
 OLIG2 is a transcription factor that regulates the development and differentiation of oligodendrocytes, influencing the process of myelination.

o Myelin Basic Protein (MBP): MBP is a major protein component of the myelin sheath produced by oligodendrocytes and is often used to identify mature oligodendrocytes and myelinated axons.
 MBP is a major protein component of the myelin sheath produced by oligodendrocytes.

o APC

Question 17

markers - M

Answer 17

o Ionized Calcium-Binding Adapter Molecule 1 (Iba1): Iba1 is a widely used marker for microglia. It is an actin-binding protein that is highly expressed in microglial cells, especially when they are activated.
 Iba1 is involved in the regulation of actin dynamics and is associated with the morphological changes that occur when microglia become activated in response to injury or inflammation.

o CD11b (Integrin Alpha M): CD11b is a cell surface marker that is commonly used to identify and isolate microglial cells in flow cytometry and immunohistochemistry.
 CD11b is a cell surface protein that is part of the complement receptor 3 (CR3) complex, which is important for microglial adhesion and phagocytosis.

Question 18

markers - S

Answer 18

o Myelin Protein Zero (MPZ, also known as P0): MPZ is another important protein found in Schwann cells and is a major constituent of the myelin sheath in the PNS.
 MPZ is a glycoprotein integral to the structure of myelin produced by Schwann cells

Question 19

neurotransmitter regulation

Answer 19

Glutamate Uptake: Astrocytes express glutamate transporters, such as GLT-1 (glutamate transporter-1) and GLAST (glutamate aspartate transporter), which are responsible for removing excess glutamate from the synaptic cleft. This uptake process ensures that glutamate does not accumulate excessively in the synapse, preventing overstimulation of neurons.

Glutamate Recycling: Once taken up by astrocytes, glutamate is converted into glutamine through the enzyme glutamine synthetase. Glutamine is then released from astrocytes and taken up by neurons. Inside neurons, glutamine is converted back into glutamate, and this process is essential for maintaining a steady supply of glutamate for neurotransmission