Neurodevelopmental disorders Flashcards
(23 cards)
Define the term neurodevelopmental disorder
a group of conditions caused by alteration in brain development
Using examples what is the difference between early-onset and late onset NDD [4]
- early onset NDD are diagnosed in childhood
- ADHD/ autism/ anxiety
- late onset NDD can only be clinically diagnosed after childhood
- depression/bipolar disorders
What are the risk factors for NDD [2]
- genetic
- environmental
Describe how cortical development may contribute to some NDDs [2]
- failures corticogenesis
- the disorder depends on timepoints are affected processes
Identify the corticogenesis processes that may result in fragile x [3]
- neurogenesis
- migration
- variety of processes
What is the role of McPH1. Relation to microcephaly [2]
- mutations in gene result in microcephaly (reduce brain size)
- leads to reduction in axons
Describe how the plane of cleavage determined the division [3]
- symmetric division leads to self-renewal of cells (equal)
- asymmetric division leads to neurogenesis (unequal)
- need balance for normal neurodevelopment
Describe the results of the study showing the importance of Mcph1 in neurodevelopment [3]
- in KO there was increased unequal (asymmetric) division
- in KO there is premature switch of progenitor from symmetric to asymmetric
- Mcph1 involved in division mode
Explain how disruption in synapse development has been associated with NDD [3]
- mutations affecting synapse organisers
- affect synaptic development
- and signalling
Describe how altered neurexins have been related to NDD [3]
- cell adhesion molecules
- altered Ca2+ channels
- lead to Timothy syndrome
What process in synaptic development is associated with fragile X syndrome
protein synthesis
Identify processes in synaptic development associated with range of NDD [5]
- scaffolding
- cell adhesion proteins
- channels and receptors
- downstream signalling
- protein homeostasis
What is the role of Shank3 [2]
- synaptic pruning
- mutation associated with range of NDD
Identify some NDDs assoatied with Shank 3 [4]
- ASD
- ID
- SCZ
- ADHD
- BD
Describe a study that showed the importance of Shank3 in synapse formation [4]
- transgenic mice where Shank3 is over expressed
- had significant increase in excitatory synapses
- leads to imbalance of excitatory/inhibitory neurones
- EEG showed transgenic mice to have hyperexcitability
Explain how disrupted synapse pruning is associated with NDD
- under/overpruning leads to inappropriate number of synapses
Overexpression of C4 is associated with which NDD
schizophrenia
What is the role of C4 [3]
- involved in compliment cascade seen in glia
- determines number of synapses microglia ‘eat’
- determines amount of pruning that occurs
Describe a study showing the role of C4 [7]
- mice control (A-) vs overexpressed C4 (A)
- markers for monocytes (CD68): high = high phagocytic activity
- and marker for microglia (Iba1)
- more phagocytic activity in mice where C4 over expressed
- less dendritic spines in A/C4 overexpressed mice
- C4 leads to excessive complement activity, decreasing number of synapses
- C4 evolved in synaptic pruning
How does C4 relate to SCZ [2]
- less synapses in SCZ
- therefore likely C4 overexpressed in SCZ
Describe how interneurone dysfunction is associated with NDD [4]
- interneurones involved in inhibition (GABAergic)
- defects lead to deficits in inhibitory development and function
- instability of neural circuits
- leads to behavioural/cognitive defects
Identify some NDDs associated with interneurone dysfunction [4]
- SCZ
- epilepsy
- Anlgeman’s syndrome
- ASD
- Down’s syndrome
- Fragile X
Identify the limitation of using organoids in NDD research [4]
- long time to develop
- can’t mimic sensory experiences that are essential for development
- can only study early stages
- don’t have non-neural/ features: microglia ventricles, myelination
- cell culturing causes chronic stress
- imperfect expression of all cell types
- lack of maturation of adult-like neural circuits
