Brain Defects and Regeneration Flashcards
What are some sources that can be used for tissue regeneration from injury? (3)
- Endogenous adult stem/precursor cells -> oligodendrocyte
- De-differentiation of somatic cells into stem/precursor cells -> newt limb re-formation
- Trans-differentiation of somatic cells into stem/precursor cells of a different lineage -> hair cells in ear following an injury
Explain the spontaneous regeneration of myelin after injury from endogenous progenitors (3)
1) Oligodendrocyte precursor cell(OPC) - existing in myelin sheath
2) injury takes place = all myelin is destroyed in this tissue
3) oligodendrocytes become activated = start restoring axon with fresh myelin
Limb regeneration in newts is achieved by … (3)
Limb regeneration in newts is achieved by de-differentiation of somatic cells in limb and muscle
The bone regrows and muscles reform, nerves grow out and innervated appropriately = new fully functioning limb
Based on the idea that these tissues (w/ loss or amputation) will dedifferentiate into pluripotent/ multi potent stem cells => which then have the ability to form all different types of tissues necessary for limb regeneration
Explain trans-differentiation of supporting cells in the ear (3)
After damage occurs in the supporting cells surrounding the hair cells = the hair cells are lost and that’s how deafness comes about.
The supporting cells have the ability to trans-differentiate into hair cells. This is using the Wnt/ beta-catenin, increased Atoh1 and mitosis.
Atoh1 is a specific tissue TF upregulator that drives these supporting cells to develop into hair cells
Why is tissue regeneration limited in most mammals including humans? (3)
Because of the inability of cells to de-differentiate, trans-differentiate
Because of the absence of suitable tissue specific stem cell reservoirs
Other systemic factors
Explain the development of the understanding of adult neurogenesis (4)
Until recently, ppl thought no new neurons are added to the brain during childhood
Endogenous neural stem cells!!!!!
1960 - evidence for neurogenesis in dentists gyrus and subventricular zone of lateral forebrain ventricles in adult brains discovered
1990s - existence of neural stem cells in these regions were demonstrated
Neurogenesis declines dramatically with age = relevance/ importance of adult neurogenesis on human brain health + function = controversial/ heavily disputed topic
Explain neurogenic niches in the adult brain (2)
The olfactory bulb contains neurogenic niches that can generate new neurons
- subventricular zone
- Subgranular zone in dentate gyrus contains neural stem cells
Explain the rostral migratory pathway (5)
1) neuroblasts are formed
2) these neuroblasts migrate across towards the front of the brain
3) this is along the rostral migratory stream
4) towards the olfactory bulb
5) then integrate into olfactory circuitry
Explain the composition of the subventricular zone (4)
It is made up of:
-B cells – self-renewing neural stem cells (astroglial cells – GFAP+, Nestin+) (symmetric)
- C cells – transit amplifying neuroblasts (asymmetric)
- A cells – migrating neuroblasts to olfactory bulb
- order also is B -> C -> A
very tightly regulated with blood vessels => suggesting that some mediators of neurogenesis might gain access + modulate neurogenesis via the bloodstream
What happens when the neuroblasts complete migration to the olfactory bulb? (3)
They:
- switch to radial migration
- differentiate into interneurons
- and integrate into the existing OB circuitry
Explain the neural stem cells found in the dentate gyrus (3)
It is made up of:
- As (stem cell)
- D (progenitor)
- G (granule neuron)
the order is As -> D -> G
They don’t migrate BUT instead remain within the DG and integrate into the hippocampal circuitry
What is the purpose of adult neurogenesis? (3)
Unlike other stem cell populations, adult neurogenesis do not
appear to have a role in repairing damage, although the
possibility that they might be used for this purpose remains
OB neurogenesis is involved in olfactory learning (eg mouse)
DG neurogenesis is required for some forms of spatial
learning, especially where a temporal component is
involved. This is referred to as “pattern separation” and defects in DG neurogenesis might be involved in post-traumatic stress disorders
Explain the link between DG neurogenesis and exercise (2)
Exercise stimulates DG neurogenesis
seen in BrdU assays in which exercise increases the BrdU expression which acts as a marker for cell proliferation - interesting to see if this will have any benefits or not
Explain the pattern of DG neurogenesis overtime(3)
Neurogenesis decreases rapidly with age
- neurogenesis peaks very early in humans
- but it rapidly declines by the 10th of one’s lifespan (7-8yrs)
What is cytoprotective function prevents NSC depletion? (3)
-Increased quiescence with age protects adult NSCs from depletion
we don’t lose the stem cells with age but instead they become quiescent -> protects them from depletion
- Increased proliferation → NSC depletion if CHD7 is deleted
- also seen that CHD7 is important reg of quiescence -> supresses the cell cycle regulators needed for quiescence
