A thread on our main findings: During my postdoc I noticed something surprising, where NLRP3-/- microglia were much better at #phagocytosis than wild-type cells even under basal (unstimulated) conditions (6) - ThreadSky

roisinmcmanus.bsky.social • 143 days ago

A thread on our main findings:
During my postdoc I noticed something surprising, where NLRP3-/- microglia were much better at #phagocytosis than wild-type cells even under basal (unstimulated) conditions (6)

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roisinmcmanus.bsky.social•143 days ago

To uncover what was driving this, we did single cell RNAseq. This unveiled a population of NLRP3-/- microglia with a strong metabolic and phagocytic signature, and the most significantly changed gene was the glutamate transporter Slc1a3 (7)

roisinmcmanus.bsky.social•143 days ago

SLC1A3 is well characterised on astrocytes. To verify the expression changes we performed bulk RNAseq on different NLRP3-/- microglia ex vivo and again saw an increase in microglial Slc1a3 (8)

roisinmcmanus.bsky.social•143 days ago

At a protein level, we observed that microglia express SLC1A3 intracellularly, and the amount was increased in NLRP3-/- cells and cortex (9)

roisinmcmanus.bsky.social•143 days ago

In contrast, in post mortem brain tissue of those with #Alzheimer’s disease who have inflammasome activation in their brain, we found reduced levels of SLC1A3 which was expressed in both microglia and astrocytes (10)

roisinmcmanus.bsky.social•143 days ago

At a functional level, NLRP3-/- microglia had increased mitochondrial activity and respiration (oxygen consumption rate – OCR) (11)

roisinmcmanus.bsky.social•143 days ago

By tracing glutamine utilisation, we observed that NLRP3-/- cells preferred to use glutamine to produce the metabolite alpha-ketoglutarate (aKG) and the concentration of aKG (downstream of glutamate) was also increased (12)

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