Astrocytes in ALS

What cells are thought to be involved in non-autonomous mechanisms of ALS?

• Motor neurons

• Astrocytes and microglia

• Motor neurons, astrocytes and microglia

• None of the above

Which of the following are functions of astrocytes in a healthy brain? Select all the correct options.

• Uptake of excess neurotransmitters, including glutamate

• Neuron myelination

• Blood-brain barrier

• Axon guidance

• Phagocytosis of cell debris

Select the correct sentence:

• Reactive astrocytes are observed in several neurodegenerative diseases, but not in ALS.

• Activated astrocytes are observed in ALS. Activated astrocytes display shrunk cell bodies and downregulation of proteins such as GFAP.

• Activated astrocytes are observed in ALS. Activated astrocytes display enlarged cell bodies and downregulation of proteins such as GFAP.

• Activated astrocytes are observed in ALS. Activated display enlarged cell bodies and upregulation of proteins such as GFAP.

Which of the following alterations have been observed in ALS astrocytes? Select all the correct answers.

• Increased production and release of pro-inflammatory mediators.

• Increased re-uptake of glutamate, which leads to excitotoxicity.

• Mitochondrial dysfunction, and increased levels of reactive oxygen species.

• Decreased proliferation rate

Select the correct sentence:

• Media conditioned by ALS astrocytes is not toxic.

• Media conditioned by ALS astrocytes is toxic but do not cause neuronal death.

• Media conditioned by ALS astrocytes is toxic and cause death of motor neurons, dorsal root ganglion neurons and GABAergic neurons.

• Media conditioned by ALS astrocytes is toxic and cause death of motor neurons, but do not affect dorsal root ganglion neurons or GABAergic neurons.

ALS astrocytes promote motor neuron death. Which of the following mechanisms may contribute to it? Select only one answer.

• Release of soluble factors that are toxic to motor neurons.

• Release of extracellular vesicles that are toxic for motor neurons.

• Release of pro-inflammatory mediators such as TGF-β1 and TNFα.

• All the above.

Transplant of healthy astrocyte precursor cells into an ALS rat model has been shown to...

• have no effect, likely due to the high level of proliferation of the toxic neurons present in the spinal cord.

• decrease motor neuron loss and extend animal survival.

Select the correct sentences:

• Activation of the Nrf2-ARE pathway in ALS models has been shown to rescue motor neuron death, and delay the onset and progression of the disease.

• Activation of the Nrf2-ARE pathway in ALS models has been shown to rescue motor neuron death, but not to affect disease onset or progression.

• Nrf2 is a master regulator of anti-inflammatory responses.

• Nrf2 is a master regulator of antioxidant responses.

Could inhibition of all pro-inflammatory mediators be a good treatment for ALS? What would be the pros and cons of this?

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