Neurobiology of resilience-Telomeres

Question 1

What are Telomeres?

(and who discovered them)

Answer 1

• Discovered in 1989 by ELizabeth Blackburn
• Telomeres are DNA-protein (shelterin) complexes located at both ends of the linear chromosomes

Question 2

What do human telomeres consist of?

Answer 2

• Tandem repeats of TTACGGG at the 3’ end of the single stranded overhang

Question 3

What do telomeres do?

Answer 3

• Protect the cells DNA from genome instability (e.g fusion between chromosomes)
• Play a crucial role in ageing
  -Extremely short telomeres induce cellular apoptosis or activates senescence

Question 4

How do telomeres decrease in length?

Answer 4

• Cumulative exposure to inflammation and oxidative stress(in dividing and non-dividing cells)
• With every mitosis

Question 5

How do telomeres increase in length?

Answer 5

• Increased by telomerase

Question 6

What is telomerase?

Answer 6

• Is a reverse transcriptase(transcribes DNA from RNA)
• Complex is made up by:
• TERT>Protein component that serves as catalytic subunit
• TERC>essential telomerase RNA component that serves as template for the elongation of a telomere
• Primary regulator of telomere length by adding telomeric DNA to telomeres

Question 7

Why are telomeres and telomerase relevant to Neuroscience?

Answer 7

• Telomerase (TERT) expression:
• High in NSC (Neuronal stem cells) and NPC (Neuronal Pyrimidal cells) in the developing and adult brain.
• Declines rapidly when STEM/progenitor cells differentiate or die
• Detected in the cytoplasm of mature (e.g. non dividing) hippocampul neurons (but in general is low in mature neurones)
• Present in activated microglia
• Absent from astrocytes

Question 8

Why are Telomeres and telomerase relevant?

(Telomerase/TERT)

Answer 8

• Telomerase activity influences cellular proliferation, differentiation, survival and apoptosis
• More than 85% of tumour cells show telomerase activation
• ALS patients have less TERT expression in their spinal cord
• Transient expression of TERT in the brain delays ALS onset and progression
• Post-mortem ALS brain has longer telomeres in microglia
• Increase in TERT expression after ischemic injury
• Upregulation of TERT in (ischemic) injured neurone, protects against NMDA excitotoxicity, decreasing neuronal death

Question 9

Need more cards

Answer 9

Yes