Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity

Maria D. Purice, Sean Speese, Mary Logan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, we explored how glial responses to neurodegeneration are altered with age. Here we show that glia-axon phagocytic interactions change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10. Importantly, boosting PI3K/Draper activity in aged glia significantly reverses slow phagocytic responses. Moreover, several hours post axotomy, early hallmarks of Wallerian degeneration (WD) are delayed in aged flies. We propose that slow clearance of degenerating axons is mechanistically twofold, resulting from deferred initiation of axonal WD and reduced PI3K/Draper-dependent glial phagocytic function. Interventions that boost glial engulfment activity, however, can substantially reverse delayed clearance of damaged neuronal debris.

Original languageEnglish (US)
Article number12871
JournalNature Communications
Volume7
DOIs
StatePublished - Sep 20 2016

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Drosophila
axons
1-Phosphatidylinositol 4-Kinase
clearances
Phosphatidylinositols
Neuroglia
Axons
Phosphotransferases
degeneration
brain
Wallerian Degeneration
acceleration (physics)
debris
Brain
disorders
Axotomy
Debris
Diptera
Neurodegenerative Diseases
interactions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity. / Purice, Maria D.; Speese, Sean; Logan, Mary.

In: Nature Communications, Vol. 7, 12871, 20.09.2016.

Research output: Contribution to journalArticle

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