Amyloid Precursor Protein in<i>Drosophila</i>Glia Regulates Sleep and Genes Involved in Glutamate Recycling

Luna, Abud J. Farca; Perier, Magali; Seugnet, Laurent

doi:10.1523/jneurosci.2826-16.2017

Cited by 54 publications

(44 citation statements)

References 65 publications

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“…A direct connection between cortex glial cells and astrocyte‐like glial cells was also demonstrated following inhibition of the Drosophila Amyloid precursor protein homolog Appl in cortex glial cells. This resulted in higher sleep amounts correlating with changes in expression in glutamine synthetase (GS) in astrocyte‐like glia and in changes in the gap‐junction component Innexin2 in cortex glia (Farca Luna, Perier, & Seugnet, ).…”

Section: Cortex Glial Cellsmentioning

confidence: 99%

Drosophila glia: Few cell types and many conserved functions

Yildirim

Petri

Kottmeier

et al. 2018

Glia

147

153

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Glial cells constitute without any dispute an essential element in providing an efficiently operating nervous system. Work in many labs over the last decades has demonstrated that neuronal function, from action potential generation to its propagation, from eliciting synaptic responses to the subsequent postsynaptic integration, is evolutionarily highly conserved. Likewise, the biology of glial cells appears conserved in its core elements and therefore, a deeper understanding of glial cells is expected to benefit from analyzing model organisms such as Drosophila melanogaster. Drosophila is particularly well suited for studying glial biology since in the fly nervous system only a limited number of glial cells exists, which can be individually identified based on position and a set of molecular markers. In combination with the well‐known genetic tool box an unprecedented level of analysis is feasible, that not only can help to identify novel molecules and principles governing glial cell function but also will help to better understand glial functions first identified in the mammalian nervous system. Here we review the current knowledge on Drosophila glia to spark interest in using this system to analyze complex glial traits in the future.

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Section: Cortex Glial Cellsmentioning

confidence: 99%

Drosophila glia: Few cell types and many conserved functions

Yildirim

Petri

Kottmeier

et al. 2018

Glia

147

153

View full text Add to dashboard Cite

show abstract

“…Similar to mammalian glia, Drosophila glia include multiple specialized cell types (Kremer, Jung, Batelli, Rubin, & Gaul, ) and are essential for neuronal development (Booth, Kinrade, & Hidalgo, ; Sepp, Schulte, & Auld, ) and maintenance (Xiong & Montell, ). In the adult nervous system, they serve many of the same specialized functions as mammalian glia, including phagocytic clearance of cellular debris (Doherty, Logan, Taşdemir, & Freeman, ; MacDonald et al, ), participation in innate immunity (Kounatidis & Chtarbanova, ), blood–brain barrier formation (DeSalvo et al, ), glutamate recycling (Farca Luna, Perier, & Seugnet, ; Rival et al, ), protection of axons in white matter (Logan et al, ), and protection of neurons from reactive oxygen species through lipid droplet formation (L. Liu, MacKenzie, Putluri, Maletić‐Savatić, & Bellen, ; L. Liu et al, ).…”

Section: Introductionmentioning

confidence: 99%

Glial α‐synuclein promotes neurodegeneration characterized by a distinct transcriptional program in vivo

Olsen

Feany

2019

Glia

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α‐Synucleinopathies are neurodegenerative diseases that are characterized pathologically by α‐synuclein inclusions in neurons and glia. The pathologic contribution of glial α‐synuclein in these diseases is not well understood. Glial α‐synuclein may be of particular importance in multiple system atrophy (MSA), which is defined pathologically by glial cytoplasmic α‐synuclein inclusions. We have previously described Drosophila models of neuronal α‐synucleinopathy, which recapitulate key features of the human disorders. We have now expanded our model to express human α‐synuclein in glia. We demonstrate that expression of α‐synuclein in glia alone results in α‐synuclein aggregation, death of dopaminergic neurons, impaired locomotor function, and autonomic dysfunction. Furthermore, co‐expression of α‐synuclein in both neurons and glia worsens these phenotypes as compared to expression of α‐synuclein in neurons alone. We identify unique transcriptomic signatures induced by glial as opposed to neuronal α‐synuclein. These results suggest that glial α‐synuclein may contribute to the burden of pathology in the α‐synucleinopathies through a cell type‐specific transcriptional program. This new Drosophila model system enables further mechanistic studies dissecting the contribution of glial and neuronal α‐synuclein in vivo, potentially shedding light on mechanisms of disease that are especially relevant in MSA but also the α‐synucleinopathies more broadly.

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“…Multiple glial subtypes have been identified that regulate sleep in Drosophila [1–3]. Moreover, glial dysfunction is associated with aging, and numerous models of neurodegeneration in flies [7–11]. Despite these bidirectional interactions between glia and sleep, surprisingly little is known about the mechanisms through which sleep-deprivation impacts glial function, and how this contributes to neurodegenerative disease.…”

Section: Resultsmentioning

confidence: 99%

Sleep regulates the glial engulfment receptor Draper to promote Wallerian degeneration

Stahl

Jaggard

Keene

2019

Preprint

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Highlights 1 2 • Sleep deprivation impairs Wallerian degeneration in fruit flies.• Pharmacological induction of sleep accelerates Wallerian degeneration.• Sleep promotes innervation surrounding damaged neurites by phagocytic glia.• Sleep increases levels of the glial activation markers Draper and Stat92E. 3 Summary 4 Sleep, a universal behavior, is critical for diverse aspects of brain function. Chronic sleep 5 disturbance is associated with numerous health consequences, including neurodegenerative 6 disease and cognitive decline. Neurite damage due to apoptosis, trauma, or genetic factors is a 7 common feature of aging, and clearance of damaged neurons is essential for maintenance of 8 brain function. In the central nervous system, damaged neurites are cleared by Wallerian 9 degeneration, in which activated microglia and macrophages engulf damaged neurons. The fruit 10 fly Drosophila melanogaster provides a powerful model for investigating the relationship 11 between sleep and Wallerian degeneration. Several lines of evidence suggest that glia influence 12 sleep duration, sleep-mediated neuronal homeostasis, and clearance of toxic substances during 13 sleep, raising the possibility that glial engulfment of damaged axons is regulated by sleep. To 14 explore this possibility, we axotomized olfactory receptor neurons and measured the effects of 15 sleep loss or gain on the clearance of damaged neurites. Mechanical sleep deprivation impaired 16 the clearance of damaged neurites, whereas the sleep-promoting drug gaboxadol accelerated 17 clearance. In sleep-deprived animals, multiple markers of glial activation were delayed, 18 including activation of the JAK/STAT pathway, upregulation of the cell corpse engulfment 19 receptor Draper, and innervation of the antennal lobe by glial membranes. These markers were 20 all enhanced when sleep was induced in gaboxadol-treated flies. Taken together, these findings 21 reveal a critical role for sleep in regulation glial activation and engulfment following axotomy, 22 providing a platform for further investigations of the molecular mechanisms underlying sleep-23 dependent modulation of glial function and neurite clearance. Results and Discussion 1 Glial regulation of synaptic function and neuronal homeostasis is critical for proper sleep [1-3]. 2The Drosophila brain contains five distinct types of glia: perineural and subperineural glia, which 3 form the blood-brain barrier; cortex glia; astrocyte-like glia, which regulate synaptic function; and 4 ensheathing glia, which surround neuropil [4][5][6]. Multiple glial subtypes have been identified that 5 regulate sleep in Drosophila [1-3]. Moreover, glial dysfunction is associated with aging, and 6 numerous models of neurodegeneration in flies [7-11]. Despite these bidirectional interactions 7 between glia and sleep, surprisingly little is known about the mechanisms through which sleep-8 deprivation impacts glial function, and how this contributes to neurodegenerative disease. 9 10 Experimental ablation of the antennae results in ax...

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Amyloid Precursor Protein inDrosophilaGlia Regulates Sleep and Genes Involved in Glutamate Recycling

Cited by 54 publications

References 65 publications

Drosophila glia: Few cell types and many conserved functions

Drosophila glia: Few cell types and many conserved functions

Glial α‐synuclein promotes neurodegeneration characterized by a distinct transcriptional program in vivo

Sleep regulates the glial engulfment receptor Draper to promote Wallerian degeneration

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