Abstract
BackgroundThe specific role of microglia on Aβ-mediated neurotoxicity is difficult to assign in vivo due to their complicated environment in the brain. Therefore, most of the current microglia-related studies employed the isolated microglia. However, the previous in vitro studies have suggested either beneficial or destructive function in microglia. Therefore, to investigate the phenotypes of the isolated microglia which exert activity of neuroprotective or destructive is required.ResultsThe present study investigates the phenotypes of isolated microglia on protecting neuron against Aβ-mediated neurotoxicity. Primary microglia were isolated from the mixed glia culture, and were further cultured to distinct phenotypes, designated as proliferating amoeboid microglia (PAM) and differentiated process-bearing microglia (DPM). Their inflammatory phenotypes, response to amyloid β (Aβ), and the beneficial or destructive effects on neurons were investigated. DPM may induce both direct neurotoxicity without exogenous stimulation and indirect neurotoxicity after Aβ activation. On the other hand, PAM attenuates Aβ-mediated neurotoxicity through Aβ phagocytosis and/or Aβ degradation.ConclusionsOur results suggest that the proliferating microglia, but not the differentiated microglia, protect neurons against Aβ-mediated neurotoxicity. This discovery may be helpful on the therapeutic investigation of Alzheimer’s disease.
Highlights
The specific role of microglia on amyloid β (Aβ)-mediated neurotoxicity is difficult to assign in vivo due to their complicated environment in the brain
Characterization of microglia phenotype and their inflammatory responses following oAβ1-42 and fAβ25-35 treatment To confirm the conformation of the prepared Aβs, the biochemical and morphological nature of fibrillary Aβ (fAβ), and oligomeric Aβ (oAβ) were studied by atomic force microscope (Figure 1)
The results suggested that ramified microglia acquired by prolonged incubation were morphologically transformed to an amoeboid phenotype by oAβ
Summary
The specific role of microglia on Aβ-mediated neurotoxicity is difficult to assign in vivo due to their complicated environment in the brain. To investigate the phenotypes of the isolated microglia which exert activity of neuroprotective or destructive is required. In the adult CNS, the number of microglia is hypothesized to be maintained via self-replication or by local progenitor cell division [2,3]. Local proliferation leads to an increased number of microglia in the spinal cord of postnatal rat [4]. Distinct phenotypic microglia has been identified to exist in specific brain regions [11,12]. Microglia may exert both protective and pathogenic functions in the CNS [13,14,15]. It is essential to identify mechanisms of activating specific microglial phenotypes that contribute to neurodegeneration to define appropriate therapeutic targets aimed at modulating microglia activities [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
