Chapter 1 Flashcards

1
Q

The original concept of Neuroglia was formed by?

A

Rudolf Virchow (mid 1800’s)

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2
Q

PNS neuroglia arises from?

A

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

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3
Q

CNS neuroglia arises from?

A

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

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4
Q

Macroglia can be divided or classified into?

A

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

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5
Q

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

A

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.

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6
Q

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

A

The maintenance of the homeostasis of the nervous system.

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7
Q

Microglia permanently reside in the CNS? True or False

A

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

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8
Q

Microglia have a main function, what is it?

A

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.

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9
Q

Does this remodeling of synapses affect processes other than homeostasis?

A

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

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9
Q

Through phagocytosis, microglia can?

A

incorporate waste products, cellular debris and pathogens.

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10
Q

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

A

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

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11
Q

Any other details microglia regulate?

A

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

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12
Q

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

A

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

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13
Q

Where do oligodendrocytes originate from?

A

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.

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14
Q

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

A

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

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15
Q

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

A

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

16
Q

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

A

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.

17
Q

How does this tie into estrogen?

A

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

18
Q

What is the general composition of myelin?

A

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

19
Q

What does this presence of cholesterol suggest?

A

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.

20
Q

Is myelin only for rapid electrical conduction?

A

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

21
Q

How does pleiotropism relate to oligodendrocytes?

A

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.

22
Q

What is the primary function of astrocytes?

A

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

23
Q

Where do astrocytes reside in the brain?

A

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

24
Q

How many subtypes of astrocytes have been identified?

A

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

25
Q

Give examples of how astrocytes maintain homeostasis?

A

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.

26
Q

Describe how they accomplish these homeostatic functions?

A

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.

27
Q

Do astrocytes integrate signals from other cells?

A

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.

28
Q

Do astrocytes contact just one other cell, or many?

A

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.

29
Q

What is the gliocrine system?

A

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.

30
Q

Which glial cells contribute to neuropathological developments?

A

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

31
Q

Name the 3 types of astrogliopathies along with their subtypes.

A

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

32
Q

Describe the subtypes of astrogliopathies

A

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.

33
Q

Can you dive into reactive astrogliosis a bit more?

A

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.

34
Q

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

A

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.

35
Q

Please describe pathological remodeling in detail.

A

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.