Chapter 1

Question 1

The original concept of Neuroglia was formed by?

Answer 1

Rudolf Virchow (mid 1800’s)

Question 2

PNS neuroglia arises from?

Answer 2

From the neural crest, classified into Schwann cells, satellite glial cells, olfactory ensheathing cells and enteric glia.

Question 3

CNS neuroglia arises from?

Answer 3

macroglia cells (ectodermal, neuroepithelial origin, microglia cells (mesodermal, myeloid origin).

Question 4

Macroglia can be divided or classified into?

Answer 4

astroglia, oligodendroglia, NG-2 glia (oligodendrocyte progenitor cells).

Question 5

The total number of neuronal and non-neuronal cells is about equal? True or False

Answer 5

True - they are almost on par with each other. Evolutionarily, this balanced ratio suggests their importance, but over time, they trended towards an increase in the ratio, thus hinting at their performance in critical cerebral functions with the largest amounts observed in whales and elephants.

Question 6

The unifying fundamental function of all types of glial cells is?

Answer 6

The maintenance of the homeostasis of the nervous system.

Question 7

Microglia permanently reside in the CNS? True or False

Answer 7

True - and they originate from a mesodermal source, and of myeloid origin, colonizing the CNS early in evolution, and are conserved across species.

Question 8

Microglia have a main function, what is it?

Answer 8

They are the resident macrophages of the brain, so their serve a heavy defensive function via their phagocytic abilities that can produce many pro/anti-inflammatory factors.

Question 9

Does this remodeling of synapses affect processes other than homeostasis?

Answer 9

Yes, this modulation of synaptic overall numbers and activity affects the processes of learning, memory and critical cognitive functions.

Question 9

Through phagocytosis, microglia can?

Answer 9

incorporate waste products, cellular debris and pathogens.

Question 10

Microglia are not fundamental for brain development, activity and plasticity? True or False

Answer 10

False, microglia are super important in all of these functions, along with the creation and remodeling of synapses.

Question 11

Any other details microglia regulate?

Answer 11

Yes, they regulate neurogenesis, neuronal density, neuronal connectivity, along with neuronal survival and turnover.

Question 12

If microglia are constantly surveying the environment, are there areas where they are particularly abundant?

Answer 12

Yes, their activities show a proclivity in regions where debris, apoptotic expression, along with areas of high density and neuronal turnover (particularly during development)

Question 13

Where do oligodendrocytes originate from?

Answer 13

OPC’s (oligodendrocyte precursor cells) that arise from multipotent neural stem cells (mNSC’s) which mostly originate from ventricular areas of the brain where they migrate to the developing CNS becoming active.

Question 14

Why does the differentiation between NG-2 glia and oligodendrocytes matter?

Answer 14

This differentiation is important for myelin repair in the adult brain, along with ensheathing new neuronal connections with myelin in response to new experiences.

Question 15

What factors modulate OPC migration, proliferation, differentiation and myelination?

Answer 15

Both extrinsic and intrinsic transcription factors, epigenetic modulators and signaling pathways.

Question 16

Do oligodendrocytes express receptors for a few classes or many? What does this suggest?

Answer 16

Many, which suggests that these cells receive inputs from impulses across many signaling pathways, which show their diversity and importance for development, normal functioning and myelination.

Question 17

How does this tie into estrogen?

Answer 17

It is suggested oligodendrocytes are favored by estrogen which prefer oligodendrocyte differentiation and myelination by regulating cholesterol homeostasis.

Question 18

What is the general composition of myelin?

Answer 18

~70% lipids (cholesterol being the primary component) and ~30% proteins (mainly myelin basic protein and proteolipid protein)

Question 19

What does this presence of cholesterol suggest?

Answer 19

The lipid used to form the myelin sheath comes from astrocytes since the BBB does not allow dietary cholesterol to enter the CNS. This means the cholesterol for the myelin is made in the brain.

Question 20

Is myelin only for rapid electrical conduction?

Answer 20

No, its also important for axonal integrity, thus meaning oligodendrocytes may provide axonal metabolic needs as they can provide glucose and lactate to axons.

Question 21

How does pleiotropism relate to oligodendrocytes?

Answer 21

The sheer number of factors in their development and function in myelination means that disrupting any one factor does not result in a loss of function.

Question 22

What is the primary function of astrocytes?

Answer 22

To maintain homeostasis and defense of the CNS. They are of the ectodermal, neuroepithelial origin.

Question 23

Where do astrocytes reside in the brain?

Answer 23

In the grey and white matter of the brain and spinal cord.

Question 24

How many subtypes of astrocytes have been identified?

Answer 24

13 (listed below): #1 - protoplasmic (grey matter) #2 - fibrous (white matter) #3 - velate (grey matter) localized in regions where neurons are densely packed and small (olfactory bulb, or granular layer of the cerebral cortex) #4 - radial glia (pluripotent neural cell precursors which mostly disappear at birth #5 - radial astrocytes (Bergmann glia, retinal Muller glia, tanycytes) #6 - pituicytes (localized in neurohypophysis) #7 - iron-enriched astrocytes (Gomori astrocytes) localized in hypothalamus and hippcampus #8 - pervascular astrocytes (endfeet connect with blood vessels, fundamental to establishing glia limitans barriers) #9 - juxtavascular astrocytes somata - close apposition with blood vessels #10 - ependymocytes - choroid plexuc cells, lining ventricles, producing CSF, along with retinal pigment epithelial cells (line up the retinal space) #11 - interlaminar astrocytes #12 - polarized astrocytes #13 - varicose projection astrocytes *Function of 11-13 still unclear

Question 25

Give examples of how astrocytes maintain homeostasis?

Answer 25

they control the levels of neurotransmitters, ions, ROS, and metabolites in the CNS. They also drive neurogenesis, regulate synaptic formation, pruning, and elimination. They also form/maintain the myelin sheath, along with controlling the BBB and blood flow. Astrocytes are best at performing their homeostatic functions.

Question 26

Describe how they accomplish these homeostatic functions?

Answer 26

They cooperate to form, through gap junctions, specific cellular networks, called syncytia, which is comprised of apposing membranes of adjacent astrocytes which are pierced by connexons. These gap junctions are highly specialized areas for the transport of 2nd messengers, ions and bioactive molecules. You can find these networks between astrocytes and oligodendrocytes in the hippocampus and neocortex.

Question 27

Do astrocytes integrate signals from other cells?

Answer 27

Yes, to carry out their homeostatic functions, they work with K+, Ca2+, NA2+ and other voltage gated channels. They express receptors for almost all types of neuroactive agents (examples: purinoreceptors, GABA receptors, ACh receptors, monoamine receptors, cannabinoid receptors, glycine receptors, and ionotropic + metabotropic Glu receptors. This allows them to control the microenvironment of the CNS.

Question 28

Do astrocytes contact just one other cell, or many?

Answer 28

Many, one astrocyte can contact several other cells, including Post-synaptic terminals, pre-synaptic terminals, oligodendrocytes, other astrocytes, and more so they can fine tune neurotransmitter levels in the synaptic cleft. They are also fundamental in the BBB being essential for protecting the BBB, controlling cerebral blood flow, and regulating the communications between the CNS and periphery.

Question 29

What is the gliocrine system?

Answer 29

a system between the glial cells and the signaling molecules that influence neuronal functional and activity, particularly focusing on hormones and how they regulate neural activity, synaptic activity, neural health and neural circuit dynamics.

Question 30

Which glial cells contribute to neuropathological developments?

Answer 30

All types contribute to neuropathologies considering their homeostatic functions and maintenance of the CNS microenvironment.

Question 31

Name the 3 types of astrogliopathies along with their subtypes.

Answer 31

1) Reactive astrogliosis -isomorphic -anisomorphic 2) Astroglial degeneration, atrophy and loss of function 3) Astrocyte pathological remodeling

Question 32

Describe the subtypes of astrogliopathies

Answer 32

1) Isomorphic - refers to changes in astrocytes that result in a more uniform or regular alteration in their structure while maintaining their overall distribution and orientation in the brain. These changes are typically reactive in nature but do not significantly alter the basic architecture of the brain tissue. 2) Anisomorphic - describes changes in astrocytes that lead to irregular or abnormal alterations in their structure, potentially including changes in orientation, distribution, or the formation of structures that disrupt the normal architecture of the brain tissue. These changes can significantly affect the function of neural circuits. 3) Pathological remodeling - Pathological remodeling in astrogliopathology refers to the process by which astrocytes undergo structural and functional changes in response to injury or disease, leading to alterations that can disrupt normal brain function. This can include changes in astrocyte morphology, proliferation, and the expression of various proteins, which may either contribute to brain repair or exacerbate pathology. 4) Degeneration/atrophy/loss of function - In the context of astrocytes, degeneration and loss of function refer to the process by which these cells lose their ability to perform their normal roles in supporting neurons, maintaining the blood-brain barrier, and regulating the brain's extracellular environment. This can lead to impaired neuronal function, disrupted synaptic communication, and increased vulnerability to injury and disease.

Question 33

Can you dive into reactive astrogliosis a bit more?

Answer 33

Originally considered the 'stereotypic' astrocyte response, can be classified as a) mild/moderate, diffuse/severe, severe with scar formation Isomorphic - reversible and keeps territorial domains for the astrocytes. Anisomorphic - does not maintain the territories, thus includes cell migration, overlap, and scar formation. The hypertrophic extensions are due to vimentin and GFAP presence (intermediate cytoskeletal filaments/proteins). Either of these is disease specific Reactive astrogliosis is evolutionarily conserved to isolate damaged regions, upregulate neuroprotection, and start the repair process of the damaged tissue, as well as the BBB. Suppression of this process tends to increase CNS damage. If sustained for too long, it can become maladaptive. Often found in AD, MS, chronic alcohol use.

Question 34

Please describe in detail astrocyte degeneration, atrophy and loss of function.

Answer 34

Morphological atrophy and functional asthenia with hallmarks being thickness and extension of astrocyte branches being reduced. Often found in SZ, OCD, MDD, etc. Can cause aberrant Glu metabolism and transport, along with Ca2+ alterations, provoking neurotransmission and excitotoxic neuronal death.

Question 35

Please describe pathological remodeling in detail.

Answer 35

Whereby astrocytes undergo modifications in their intracellular space, affecting intracellular cascade signaling or functional properties making them pathological. Often found in the progression of neurological diseases. Can affect white matter - particularly leukodystrophies. Often the results of accumulation of substances in the myelin that gradually destroy the myelin.