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...
Guardado en:
Autores principales: | , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2018
|
Materias: | |
Acceso en línea: | https://doaj.org/article/722c2f62e15647dca9f8e86af5410c9f |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:722c2f62e15647dca9f8e86af5410c9f |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT saramerlo thecontributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT simonafedericaspampinato thecontributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT martinabeneventano thecontributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT mariaangelasortino thecontributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT saramerlo contributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT simonafedericaspampinato contributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT martinabeneventano contributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath AT mariaangelasortino contributionofmicrogliatoearlysynapticcompensatoryresponsesthatprecedebamyloidinducedneuronaldeath |
_version_ |
1718388258793062400 |