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Amyloid-β Inhibits Thrombospondin 1 Release From Cultured Astrocytes: Effects on Synaptic Protein Expression
| Content Provider | Scilit |
|---|---|
| Author | Rao, Kakulavarapu V. Rama Curtis, Kevin Johnstone, Joshua T. Norenberg, Michael D. |
| Copyright Year | 2013 |
| Description | Journal: Journal of Neuropathology and Experimental Neurology Among the consequences of Alzheimer disease are disturbances in synaptic integrity that ultimately lead to impaired cognitive functions. Thrombospondins are extracellular matrix proteins that, in the CNS, are predominantly produced by astrocytes and have been implicated in synaptogenesis. This study examined the effects of amyloid-β $(Aβ_{1–42}$; Aβ) peptide on intracellular and extracellular levels of thrombospondin 1 (TSP-1) in cultured astrocytes. Amyloid-β caused a significant (1- to 3-fold) increase in astrocytic intracellular levels of TSP-1 (increased retention) that was associated with a reduction of its release from astrocytes. Because Aβ is known to induce oxidative stress in astrocytes, we examined the effects of the antioxidants tempol and apocynin on astrocytic TSP-1 levels and release. Treatment of Aβ-exposed astrocyte cultures with antioxidants significantly diminished its cellular retention and stimulated its release. Furthermore, the addition of conditioned media derived from Aβ-treated cultured astrocytes that contained a reduced TSP-1 content resulted in a significant loss of synaptophysin and PSD95 in cultured neurons. These findings suggest that Aβ-mediated reduction in astrocytic TSP-1 release, possibly related to oxidative stress, contributes to the loss of synaptophysin in neurons. Strategies aimed at enhancing the astrocytic release of TSP-1 may have a therapeutic benefit in Alzheimer disease. |
| Related Links | https://academic.oup.com/jnen/article-pdf/72/8/735/9562901/72-8-735.pdf http://jnen.oxfordjournals.org/content/jnen/72/8/735.full.pdf |
| Ending Page | 744 |
| Page Count | 10 |
| Starting Page | 735 |
| ISSN | 00223069 |
| e-ISSN | 15546578 |
| DOI | 10.1097/nen.0b013e31829bd082 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Issue Number | 8 |
| Volume Number | 72 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2013-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neuropathology and Experimental Neurology Cultured Astrocytes |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Neurology (clinical) Pathology and Forensic Medicine Cellular and Molecular Neuroscience |
