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Biological Foundations of Mental Health > Microanatomy of the nervous system > Flashcards

Microanatomy of the nervous system Flashcards

1
Q

Why did Santiago Ramon y Cajal and Camillo Golgi were jointly awarded the Nobel Prize of physiology and medicine in 1906?

A

For their discovery that the brain is not a single continuous system, but composed of individual cell units.

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2
Q

What makes the different types of neurons?

What are these types?

A

Many forms of neurons specialised for their particular function within the nervous system

  • Sensory neurons: can be activated by changes in skin cells
  • Motor neurons: stimulate muscle movement
  • Local interneurons: send and receive signals with multiple other neurons
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3
Q

What are the glial subtypes?

A

> Astrocytes
Microglia
Oligodendrocytes
Ependymal cells

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4
Q

What is the role of ependymal cells?

A

Line the ventricles of the brain and the central canal of the spinal cord.

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5
Q

What is the relation between neurons and glial cells?

A

Neurons are supported by different types of glia.

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6
Q

What is the role of astrocytes?

A

> Physical scaffolding framework for neurons
Distribute nutrients from the blood supply to neurons
Help maintain blood-brain barrier
Tissue repair -> glial scars
Regulation of synaptic activity by direct contact with synapses
Astrocyte-astrocyte signalling via gap junctions

> Help maintain optimal microenvironment around neurons

  • potassium (K) buffer after depolarisation
  • metabolize and recycle NTs: especially Glu (toxic extracellularly)
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7
Q

What is the role of microglia?

A

> CNS macrophages
Resident immune cells of brain = immunosuppressed stable population
Clear cellular debris -> degrade synapses
- essential for synaptic pruning during development, BUT makes matters worse by preventing recovery when neurons undergo chronic stress during disease
- apoptosis

> Recruit other cells to sites of damage
- assist activated T cells

> Aid in tissue repair

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8
Q

What are macrophages?

A

Primary mediators of granulomatous inflammation

- M1 macrophages are activated for cell mediated immune response to provide host defence

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9
Q

What are T cells?

A

T cells are central regulators of the immune response

  • modulate the function of other immune cells
  • affect the behaviour of endothelial and parenchymal cells
  • express membrane-bound molecules and secrete soluble mediators -> control antibody responses, activate innate immune cells, and lyse target cells
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10
Q

What is the role of oligodendrocytes?

A

> Support and insulate neuronal axons by generation of myelin sheath in CNS (vs. Schwann cells in PNS)
-> increased speed of neuronal signalling through saltatory conduction

> Provide metabolic support

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11
Q

What is the difference between oligodendrocytes and Schwann cells?

A

> Oligodendrocytes form myelin sheath on neuronal axons in the Central Nervous System (CNS)
Schwann cells form myelin sheath on neuronal axons in the Peripheral Nervous System (PNS)

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12
Q

What is the impact of demyelinating diseases, such as multiple sclerosis?

A

Cause degeneration of the myelin sheath, which prevents the brain from communicating properly with the body.

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13
Q

What is characteristic of the difference between acute and chronic neuroinflammation?

A

There is a delicate balance between:

  • an Acute neuroinflammation inducing a defence response,
  • and a Chronic neuroinflammation inducing an over/aberrant activation of astrocytes and microglia

> Altered function of glial cells -> disturbed synaptic transmission

=> Dysfunction can result in vulnerability to neurodevelopment and neurodegenerative diseases

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14
Q

What does the extent of dendritic branching reflect?

A

The neurone’s required level of input

- dendrites are the main site of neuronal input

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15
Q

What does axonal length determine?

Which neurons have long axons?

A

The distance of ouput in the network

  • motor neurons have long axons
    e. g. longest axon from lower motor neuron cell body in spinal cord to control the muscles in your big toe = 1m
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16
Q

What are dendritic spines?

A

Small protrusions on dendrites which form the postsynaptic side of a synapse, receiving input from another neuron

  • their shape and size will affect the receive and transmit input
  • spines with larger surface area form stronger, more stable synapses
  • spines are ‘plastic’: increase in size during learning and memory
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17
Q

What is characteristic of microglial morphology?

A

Microglial change morphology when they become activated or ‘reactive’:

  • progressively become round and phagocytic
  • reactive microglia release more cytokine to attract more microglia to the site of perceived injury
  • in phagocytic mode, they consume any perceived debris, which can include synapses
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18
Q

What is a phagocyte?

A

Type of cell with ability to ingest and digest foreign particles (e.g. bacteria, dust, dye)

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19
Q

What are cytokines?

A

Polypeptides secreted by leukocytes and other cells that act principally on hematopoietic cells

  • the effects of which include modulation of immune and inflammatory responses
  • their concentrations vary during the course of a disease
  • pro- or anti-inflammatory effects, and these effects can be contextual
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20
Q

What is characteristic of astrocytic morphology?

What is astrocytosis?

A

It is highly variable, even at rest
- activation is therefore often inferred through astrocytosis: an increased number of cells in a given location (due to recruitment or proliferation of astrocytes)

21
Q

How can microglial and astrocytic morphologies be used?

A

To score and infer neuroinflammation (Ghazi-Noori et al., 2012):
> the mouse model of frontotemporal dementia shows progressive neuroinflammation (vs. non-transgenic mouse control) when stained with anti-microglial (Iba1) antibody

> Increased coverage of staining for an astrocytic marker (GFAP) infers astrocytosis in a mouse model of frontotemporal dementia (vs. non-transgenic mouse control)

22
Q

What is common of all cells?

What are the 2 broad categories of cells?

A

All cells have a cell membrane, a cytoplasm (belly fluid), and DNA

  1. Eukaryotic cells
    - they have a nucleus and membrane-enclosed organelles (‘little organs’)
    - they are complex cells found in plants and animals
    (e. g. neurons)
  2. Procaryotic cells -> unicellular organisms (e.g. bacteria)
    - no nucleus or membrane-enclosed organelles
    - they have DNA, but not contained in a nucleus
23
Q

What are the neuronal substructures (organelles)?

A 
> Nucleus
> Endoplasmic reticulum
> Golgi apparatus
> Mitochondria
> Lysosome
> Cell membrane
24
Q

What is the function of a nucleus?

A

Genetic code store

- contains a nucleolus which generates ribosomes that synthesise proteins after leaving the nucleus

25
Q

What are the two types of endoplasmic reticulum?

What is its function?

A

> Rough endoplasmic reticulum (rER): with ribosomes
Smooth endoplasmic reticulum (sER): no ribosomes

> Produce proteins, sort and process them for delivery to their required location

26
Q

What is the function of the Golgi apparatus?

A

Additional sorting and processing centre for proteins

27
Q

What is the function of the mitochondria?

A

Energy generator

  • cellular respiration -> synthesise ATP molecules for energy
  • role in calcium buffering and cell signalling
28
Q

What is the function of the lysosome?

A

Degrades proteins and organelles when faulty

- “garbage collectors”: filled with enzymes that breakdown cellular debris

29
Q

What is the function of cell membrane?

A

It’s a lipid bilayer containing receptors for cellular communication

30
Q

What is the process of protein synthesis?

A

Proteins emerge in vesicles from the endoplasmic reticulum ;
the Golgi apparatus receives them and renders them usable by the cell
- by folding them into usable shapes or adding material to them (lipids or carbohydrates)

31
Q

What are the 3 unique features of a neuron?

A
  1. Unusually high energy demand
    - brain uses 20% of the consumed oxygen
    - biggest ATP (energy) demand -> sodium-potassium ATP pump (Na+ / K+-ATPase) which maintains electrical equilibrium of its membrane
    - other demands: recycling NTs ; calcium (Ca2+) buffering
  2. Need to transport cargo along long distances (due to its extended morphology)
    - proteins and mitochondria are produced next to nucleus, BUT required at distant sites (e.g. synapses)
    - cargo needs to be transported back to the soma for recycling and signalling
    - transport occurs along microtubules, in a balance between anterograde and retrograde transport
    - > anterograde transport = away form cell body
    - > retrograde transport = towards cell body
  3. Vulnerable to stress
    - we have a limited capacity to generate new neurons
    - neurons cannot undergo cell division for growth or repair
    - neurons become vulnerable with age as cell components deteriorate
32
Q

What is adenosine triphosphate (ATP)?

A
  • Energy transfer molecule
  • Phosphate donor
  • Signalling molecule
33
Q

Which key neuronal processes become dysfunctional with ageing?

A
  • Protein clearance
  • DNA repair
  • Mitochondrial dysfunction
34
Q

What is the possible reason why there is selective vulnerability of distinct neuronal populations / brain regions in different neurological diseases?

A

Differences in the resistance of particular neurons to different cell/network stressors

35
Q

Why do neurons have a high protein content?

A

The neurone’s ability to renew protein content is essential for maintaining cell health and allowing plasticity
- protein renewal can occur through protein synthesis and recycling

36
Q

What is neuronal plasticity?

A

The key ability of neurons to adapt to stimuli.

37
Q

What is gene expression?

A

The process by which a gene (DNA) is used to synthesise the product it encodes

  • mostly protein, but also functional ribonucleic acids (RNAs)
    e. g. transfer RNA (tRNA) and ribosomal RNA (rRNA)
38
Q

What is protein synthesis?

A

How gene expression generates new protein from the genetic code.

39
Q

What are the steps of protein synthesis?

A

> Transcription: photocopying DNA into RNA (mRNA)
-> DNA is preserved in the nucleus

> RNA splicing

> Translation, of the genetic code on the mRNA photocopy into protein

40
Q

What happens during the transcription phase of protein synthesis?

A

> RNA polymerase enzyme copies DNA code (A, G, C, T) into mRNA (A, G, C, U)

> DNA structure is normally condensed and must be relaxed so the transcription factors can bind and initiate transcription
- epigenetic, e.g. DNA methylation, can control whether DNA structure can be relaxed
(DNA methylation; addition of methyl group to DNA)

41
Q

What is the role of RNA splicing?

What does alternative splicing allow?

A

> Prior to translation
messenger RNA contains both coding (exons) and non-coding regions (introns)
Splicing machinery cuts out introns
-> Mature RNA (mRNA) contains only protein-coding regions

> Alternative splicing can produce different proteins from a single mRNA
-> DNA can increase the number of potential proteins it makes

> Mature mRNA is then exported from the nucleus to the cytoplasm for translation into protein

42
Q

What is the role of RNA sequencing?

A

Assesses gene expression at the mature RNA level

- informs which genes are actively transcribed and how they spliced

43
Q

What happens during the translation phase of protein synthesis?

A

> Ribosomes translate RNA into protein
3 base-pair code = 1 amino acid (ATG = start)
Transfer RNA (tRNA) brings amino acids into the ribosome where they are bound together to form a polypetide chain = protein
-> when folded into the correct structure becomes a functional protein

44
Q

What is local translation?

A

Translation occurring far away from the nucleus, at sites with high demand, such as synapses
(translation normally occurs close to the nucleus)

45
Q

What are amino acids?

A

Natural compounds composed of an amine group (–NH2) and a carboxylic acid group (–COOH), linked to the same carbon atom
- key elements: carbon, hydrogen, oxygen, nitrogen

46
Q

What are polypeptides?

A

Polypeptides are biomaterials composed of repeating amino acid units linked by a peptide bond.

47
Q

What are peptides?

A

Peptides are short chains made up of amino acid monomers linked by amide bonds
- often obtained from the breakdown of proteins

48
Q

What is protein folding?

A

> Occurs as soon as a protein is made
Folding undergoes quality control to ensure it is correct
- misfolded proteins -> degradation

> Post-translational modification of proteins can modulate their folding and function (e.g. phosphorylation)
-> increasing diversity of protein functionality -> different protein activity during different cellular activities

49
Q

What is the consequence of protein misfolding and accumulation?

A

Major cause of neurodegenerative disease

- increase in disease due to genetic mutations, cellular stress, and impairment of protein clearance

Biological Foundations of Mental Health (30 decks)

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