Neuroinflammation in alcoholism

Question 1

What are the 3 types of drinking problem?

Answer 1

Hazardous (BP too high etc)

Problem drinking

Dependent drinking
(see criteria)

Question 2

What are the 2 ends of the alcohol brain damage spectrum?

Answer 2

Wernicke-Korsakoff syndrome to subtle cognitive dysfunction.

Question 3

What are the multiple factors of alcohol related brain damage?

Answer 3

Thiamine deficiency
Direct neurotoxicity
Microvascular disease
Liver disease
Multiple withdrawal episodes
Head injury

Question 4

What is the difference in expression of microglia and inflammatory cytokines in alcohol dependent tissue vs controls?

Answer 4

Increased expression in alcoholic tissue.

Question 5

Via which receptors do alcohol activate microglia?

Answer 5

TLR4.

Question 6

What other effect does cytokines have in the brain?

Answer 6

Cause behavioural and mood changes.

Question 7

What are the steps in PET imaging?

Answer 7

Inject radiotracer with target molecule. Start scan. Radioligands decay and map time activity curves for each brain region. Cross the BBB and bind to target, positron and electron collide and use imaging to detect where this occurred. Analyse with computers.

Question 8

What is the target in imaging microglia?

Answer 8

Binds TSPO. This has different binding affinities.

Question 9

What inflammatory cytokine had a relationship with withdrawal and depression.

Answer 9

IL-6: Positive relationship with withdrawal symptoms and depression at all time points.

Question 10

What is the link between alcohol and Alzheimers?

Answer 10

Alcohol increases risk.

Question 11

How does amyloid bidn to microglia and what does this cause?

Answer 11

Binds to TLR4 receptor, causing cytokine and chemokine release. This causes neurodegeneration and cell death.

Question 12

What was done in the Alcamy study?

Answer 12

Alcohol dependent participants and healthy controls.

Amyloid load imaged. Florbetapir tracer used, which binds to B-amyloid. Levels in vivo correated.