Methods to Study NDDs Flashcards

(34 cards)

1
Q

Give examples of NDDs

A
  • intellectual disability
  • communication disorders
  • autism spectrum disorder
  • ADHD
  • neurodevelopmental motor disorders
  • specific learning disorders
  • schizophrenia
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2
Q

What are the DSM-5?

A

a group of conditions with onset in the developmental period, inducing deficits that produce impairments of functioning

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3
Q

What causes neurodevelopmental disorders?

A

disruption of formation of neuronal networks

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4
Q

What causes neurodegenerative disorders?

A

disruption of established neuronal networks

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5
Q

What is the time of onset of degenerative disorders?

A

after neuronal circuits have been formed

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6
Q

Give examples of degenerative disorders

A
  • AD
  • PD
  • HD
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7
Q

Give examples of developmental disorders

A
  • autism
  • ADHD
  • anxiety disorders
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8
Q

What does the time of onset of developmental disorders correlate to?

A

development of the brain

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9
Q

Which developmental stages are affected by neurodevelopmental diseases?

A
  • neurogenesis
  • neuronal migration
  • neuronal differentiation
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10
Q

Which biological processes are affected by neurodevelopmental diseases?

A
  • regulation of protein synthesis
  • regulation of transcription
  • epigenetic regulation
  • synaptic signalling
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11
Q

Give examples of common themes between human NDDs

A

changes in neuronal networks and synaptic function

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12
Q

What are synaptopathies?

A

brain disorders with underlying synaptic dysfunction that result from alterations in intrinsic synaptic molecular mechanisms

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13
Q

What are causes of synaptopathies?

A
  • mutations of synaptic genes
  • mutations of genes involved in neuronal and synapse development
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14
Q

What are the 8 steps of synaptic transmission?

A
  1. synaptic vesicle loading
  2. docking
  3. priming
  4. vesicle fusion
  5. clathrin-mediated endocytosis
  6. uncoating
  7. endosome fusion
  8. synaptic vesicle reformation
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15
Q

What does the postsynaptic density do?

A

mediate clustering of receptors and cell-adhesion molecules and orchestrate the coupling of diverse signalling components

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16
Q

Give examples of implicated presynaptic genes

A
  • synapsins
  • synaptophysin
  • piccolo
  • SNAP25
  • cadherin
17
Q

Give examples of implicated postsynaptic genes

A
  • neuroligin 3 and 4
  • neurexin 1
  • ApoE e4 allele
  • calcineurin
18
Q

What are dendritic spines?

A

tiny protrusions from dendrites, which form functional contacts with neighbouring axons of other neurons and receive input from one excitatory synapse

19
Q

What do dendritic spines do?

A
  • implement input-specific synaptic plasticity
  • enhance synaptic connectivity
  • modify synaptic potentials
20
Q

What do dendritic spines represent?

A

excitatory postsynaptic compartments

21
Q

What is synaptic pruning?

A

he process in which the brain removes neurons and synapses that it does not need (normally happens between age 2-10)

22
Q

What changes in neuropsychiatric disorders?

A

spine density

23
Q

What do changes in spine density affect?

A

neuronal networks

24
Q

What do guidance cues do?

A

wire neurons into networks

25
What is the first step in studying synaptopathies?
identifying the genes involved
26
How can specific genes be identified?
- forward genetics (mutagenesis, positional cloning) - reverse genetics (ectopic expression, gene silencing, gene targeting) - GWAS - whole genome sequencing
27
Give examples of models used to study synaptic disorders
- 2D cell cultures - C. elegans - drosophila - zebrafish - mouse - human organoids
28
Give examples of methods used to study synaptopathies
- synaptosomes/synaptoneurosome isolation - neuropil microdissection - axon-TRAP - fluorescent activation cell sorting for synaptosomes - puromycin proximity ligation assay - expansion sequencing
29
Give examples of microscopic strategies for studying synapses
- enumeration of spine density and morphologies - investigation of synaptic marker distribution - investigating nanoscale synaptic organisation - whole cell / single synapse imaging of synaptic transmission - electrophysiology
30
How can axons and dendrite development be viewed?
Sholl analysis
31
What happens during Sholl analysis?
concentric ircles are superimposed on the dendritic processes and at each point of intersection, the number of crosses is counted to produce a plot
32
What do brain organoids do?
capture the key features of human brain development and organisation
33
What can brain organoids be used for?
precision medicine
34
What are the limitations of organoid technologies?
- cellular components - standardisation - costly - scalability issues - heterogeneity - lack of output compared to whole organisms