TGF‐β2 and TGF‐β3 from cultured β‐amyloid‐treated or 3xTg‐AD‐derived astrocytes may mediate astrocyte–neuron communication. (18th January 2018)

• Record Type: Journal Article
• Authors: Tapella, Laura; Cerruti, Matteo; Biocotino, Isabella; Stevano, Alessio; Rocchio, Francesca; Canonico, Pier Luigi; Grilli, Mariagrazia; Genazzani, Armando A.; Lim, Dmitry
• Is Part Of: European journal of neuroscience. Volume 47:Number 3(2018)
• Page Start: 211
• Page End: 221
• Publication Date: 2018-01-18
• Subjects: Alzheimer's disease -- calcineurin -- neurodegeneration -- PSD95; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13819
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF‐β) TGF‐β1, TGF‐β2 and TGF‐β3. TGF‐β1 is the most studied isoform, while production and release of TGF‐β2 and TGF‐β3 by astrocytes have been poorly characterized. Here, we report that purified cultures of hippocampal astrocytes produce mainly TGF‐β3 followed by TGF‐β2 and TGF‐β1. Furthermore, astrocytes release principally the active form of TGF‐β3 over the other two. Changes in release of TGF‐β were sensitive to the calcineurin (CaN) inhibitor FK506. Starvation had no effect on TGF‐β1 and TGF‐β3 while TGF‐β2 mRNA was significantly up‐regulated in a CaN‐dependent manner. We further investigated production and release of astroglial TGF‐β in Alzheimer's disease‐related conditions. Oligomeric β‐amyloid (Aβ) down‐regulated TGF‐β1, while up‐regulating TGF‐β2 and TGF‐β3, in a CaN‐dependent manner. In cultured hippocampal astrocytes from 3xTg‐AD mice, TGF‐β2 and TGF‐β3, but not TGF‐β1, were up‐regulated, and this was CaN‐independent. In hippocampal tissues from symptomatic 3xTg‐AD mice, TGF‐β2 was up‐regulated with respect to control mice. Finally, treatment with recombinant TGF‐βs showed that TGF‐β2 and TGF‐β3 significantly reduced PSD95 protein in cultured hippocampal neurons, and this effect was paralleled by conditioned media from Aβ‐treated astrocytes or from astrocytes from 3xTg‐AD mice. Taken together, our data suggest that TGF‐β2 and TGF‐β3 are produced by astrocytes in a CaN‐dependent manner and should be investigated further in the context of astrocyte‐mediated neurodegeneration. Abstract : Aβ42 ‐treated astrocytes and astrocytes from 3xTg‐AD mice increase TGF‐β2 and TGF‐β3. TGF‐β2 and TGF‐β3 reduce PSD95 protein in cultured hippocampal neurons, and the same effect is observed with conditioned medium from 3xTg‐AD‐ or Aβ42 ‐treated astrocytes. Alongside other factors, astroglial TGF‐β2 and TGF‐β3 may contribute to neurodegeneration in Alzheimer's disease.