Astrocytes and Damage

Question 1

Mishra (2016)

Answer 1

Blocked astrocyte calcium elevations in cortical brain slices with BAPTA- reduction in the dilation of capillaries - no effect on arterioles.

Question 2

Kraft (2013)

Answer 2

Transgenic mouse line with Gfap and Vim intermediate filament proteins required for astrocyte activation deleted on model AD background (APP/PS1). Gene deletions increased amyloid placque load

Question 3

Liu (2017)

Answer 3

cKO of LRP1 in astrocytes on amyloid model background revealed clear role in Abeta clearance. Controversial whether it directly binds, but ApoE is also a critical LRP1 ligand, therefore may compete with Abeta for cellular uptake into astrocytes.

Question 4

Allaman (2010)

Answer 4

Cultured astrocytes exposed to Abeta. Increase in glucose uptake seen + ROS generation. Modification of astrocyte metabolism shown to impair neuronal viability in astrocyte-neuronal co-cultures.

Question 5

Orre (2014)

Answer 5

Isolation of reactive astrocytes and microglia from mouse model of AD with enhanced expression of PSEN1 and APP. Pro-inflammatory phenotype, and reduced expression of neuronal support genes. Abeta induced astrocyte reactivity may comprimise astrocyte function.

Question 6

Zhao (2013)

Answer 6

Combination treatment with anti-Nogo-A and chondroitinase ABC in rat dorsal column lesion model promoted significant functional recovery in forelimb reaching task.

Question 7

Zhao (2013) critique

Answer 7

Partial lesion model not gold standard- plasticity vs regeneration.

Question 8

Sorfroniew (2016)

Answer 8

Prevented astrocyte scar formation with GCV-inducible destruction of astrocytes in mouse model of SCI (weight drop). Mice without astrocyte activity failed to form scars, exhibited larger areas of damage with little axonal regrowth. CSPGS may be produced by other cells.

Question 9

What other roles do Astrocytes have in SCI? (3)

Answer 9

• clear excitotoxic glutamate
• degrade Abeta
• stabilise extracellular fluid and ion balance.

Question 10

What is important to remember about astrogliosis?

Answer 10

Spectrum of heterogenous potential changes, determined by context-specific factors through diverse signalling events.

Question 11

Faulkner (2004)

Answer 11

Transgenic LOF study on newly proliferated scar astrocytes through GFAP HSV-TK construct. Revealed astrocytes repair BBB and restrict inflammation.