PMID- 29740062 OWN - NLM STAT- MEDLINE DCOM- 20191014 LR - 20231112 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 May 8 TI - The contribution of microglia to early synaptic compensatory responses that precede beta-amyloid-induced neuronal death. PG - 7297 LID - 10.1038/s41598-018-25453-1 [doi] LID - 7297 AB - Glial-neuronal cross-talk has a critical role in the development of neurodegenerative conditions, including Alzheimer's Disease, where it affects neuronal responses to beta-amyloid peptide (Abeta)-induced toxicity. We set out to identify factors regulating synaptic responses to Abeta, dissecting the specific role of glial signaling. A low concentration of aggregated Abeta42 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 Abeta42-treated (CMA) microglia were tested for their effects on synaptophysin expression in SH-SY5Y neuronal-like cells during challenge with Abeta42. Both CMC and CMA prevented Abeta-induced synaptophysin loss. In the presence of Abeta + 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 Abeta42-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 Abeta synaptotoxicity, which potentially lead to their extended survival. FAU - Merlo, Sara AU - Merlo S AD - Department of Biomedical and Biotechnological Sciences, section of Pharmacology, University of Catania, Catania, Italy. FAU - Spampinato, Simona Federica AU - Spampinato SF AD - Department of Biomedical and Biotechnological Sciences, section of Pharmacology, University of Catania, Catania, Italy. FAU - Beneventano, Martina AU - Beneventano M AD - Department of Biomedical and Biotechnological Sciences, section of Pharmacology, University of Catania, Catania, Italy. FAU - Sortino, Maria Angela AU - Sortino MA AUID- ORCID: 0000-0002-2734-1521 AD - Department of Biomedical and Biotechnological Sciences, section of Pharmacology, University of Catania, Catania, Italy. msortino@unict.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180508 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Peptide Fragments) RN - 0 (Synaptophysin) RN - 0 (amyloid beta-protein (1-42)) SB - IM MH - Alzheimer Disease/*drug therapy/metabolism/pathology MH - Amyloid beta-Peptides/genetics/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cell Death/drug effects MH - Cells, Cultured MH - Culture Media, Conditioned/chemistry/pharmacology MH - Gene Expression Regulation/drug effects MH - Hippocampus/drug effects/pathology MH - Humans MH - Microglia/drug effects/metabolism MH - Neuroglia/drug effects/pathology MH - Neurons/*drug effects/pathology MH - Neuroprotection/genetics MH - Peptide Fragments/genetics/pharmacology MH - Rats MH - Synapses/*drug effects/pathology MH - Synaptophysin/pharmacology PMC - PMC5940848 COIS- The authors declare no competing interests. EDAT- 2018/05/10 06:00 MHDA- 2019/10/15 06:00 PMCR- 2018/05/08 CRDT- 2018/05/10 06:00 PHST- 2017/12/14 00:00 [received] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/05/10 06:00 [entrez] PHST- 2018/05/10 06:00 [pubmed] PHST- 2019/10/15 06:00 [medline] PHST- 2018/05/08 00:00 [pmc-release] AID - 10.1038/s41598-018-25453-1 [pii] AID - 25453 [pii] AID - 10.1038/s41598-018-25453-1 [doi] PST - epublish SO - Sci Rep. 2018 May 8;8(1):7297. doi: 10.1038/s41598-018-25453-1.