The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death

Abstract Glial-neuronal cross-talk has a critical role in the development of neurodegenerative conditions, including Alzheimer’s Disease, where it affects neuronal responses to β-amyloid peptide (Aβ)-induced toxicity. We set out to identify factors regulating synaptic responses to Aβ, dissecting the...

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Auteurs principaux:	Sara Merlo, Simona Federica Spampinato, Martina Beneventano, Maria Angela Sortino
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2018
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/722c2f62e15647dca9f8e86af5410c9f
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spelling	oai:doaj.org-article:722c2f62e15647dca9f8e86af5410c9f2021-12-02T15:08:13ZThe contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death10.1038/s41598-018-25453-12045-2322https://doaj.org/article/722c2f62e15647dca9f8e86af5410c9f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25453-1https://doaj.org/toc/2045-2322Abstract Glial-neuronal cross-talk has a critical role in the development of neurodegenerative conditions, including Alzheimer’s Disease, where it affects neuronal responses to β-amyloid peptide (Aβ)-induced toxicity. We set out to identify factors regulating synaptic responses to Aβ, dissecting the specific role of glial signaling. A low concentration of aggregated Aβ42 induced selective up-regulation of mature brain-derived neurotrophic factor (BDNF) expression and release in rat organotypic hippocampal cultures as well as in cortical pure microglia. Conditioned media from resting (CMC) or Aβ42-treated (CMA) microglia were tested for their effects on synaptophysin expression in SH-SY5Y neuronal-like cells during challenge with Aβ42. Both CMC and CMA prevented Aβ-induced synaptophysin loss. In the presence of Aβ + CMA, synaptophysin was over-expressed, although it appeared partly clumped in cell bodies. Synaptophysin over-expression was not directly dependent on BDNF signaling on neuronal-like cells, but relied on autocrine BDNF action on microglia. FM1-43 labeling experiments revealed compromised synaptic vesicle recycling in Aβ42-treated neuronal-like cells, rescued by microglial conditioned medium. In these conditions, significant and prolonged neuroprotection was observed. Our results point to microglia as a target for early intervention, given its positive role in supporting neuronal compensatory responses to Aβ synaptotoxicity, which potentially lead to their extended survival.Sara MerloSimona Federica SpampinatoMartina BeneventanoMaria Angela SortinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Merlo Simona Federica Spampinato Martina Beneventano Maria Angela Sortino The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
description	Abstract Glial-neuronal cross-talk has a critical role in the development of neurodegenerative conditions, including Alzheimer’s Disease, where it affects neuronal responses to β-amyloid peptide (Aβ)-induced toxicity. We set out to identify factors regulating synaptic responses to Aβ, dissecting the specific role of glial signaling. A low concentration of aggregated Aβ42 induced selective up-regulation of mature brain-derived neurotrophic factor (BDNF) expression and release in rat organotypic hippocampal cultures as well as in cortical pure microglia. Conditioned media from resting (CMC) or Aβ42-treated (CMA) microglia were tested for their effects on synaptophysin expression in SH-SY5Y neuronal-like cells during challenge with Aβ42. Both CMC and CMA prevented Aβ-induced synaptophysin loss. In the presence of Aβ + CMA, synaptophysin was over-expressed, although it appeared partly clumped in cell bodies. Synaptophysin over-expression was not directly dependent on BDNF signaling on neuronal-like cells, but relied on autocrine BDNF action on microglia. FM1-43 labeling experiments revealed compromised synaptic vesicle recycling in Aβ42-treated neuronal-like cells, rescued by microglial conditioned medium. In these conditions, significant and prolonged neuroprotection was observed. Our results point to microglia as a target for early intervention, given its positive role in supporting neuronal compensatory responses to Aβ synaptotoxicity, which potentially lead to their extended survival.
format	article
author	Sara Merlo Simona Federica Spampinato Martina Beneventano Maria Angela Sortino
author_facet	Sara Merlo Simona Federica Spampinato Martina Beneventano Maria Angela Sortino
author_sort	Sara Merlo
title	The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
title_short	The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
title_full	The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
title_fullStr	The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
title_full_unstemmed	The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
title_sort	contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/722c2f62e15647dca9f8e86af5410c9f
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The contribution of microglia to early synaptic compensatory responses that precede β-amyloid-induced neuronal death

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