Astrocyte truncated tropomyosin receptor kinase B mediates brain-derived neurotrophic factor anti-apoptotic effect leading to neuroprotection

Journal of Neurochemistry
Julieta SabaCarla Caruso

Abstract

Astrocytes are glial cells that help maintain brain homeostasis and become reactive in neurodegenerative processes releasing both harmful and beneficial factors. We have demonstrated that brain-derived neurotrophic factor (BDNF) expression is induced by melanocortins in astrocytes but BDNF actions in astrocytes are largely unknown. We hypothesize that BDNF may prevent astrocyte death resulting in neuroprotection. We found that BDNF increased astrocyte viability, preventing apoptosis induced by serum deprivation by decreasing active caspase 3 and p53 expression. The anti-apoptotic action of BDNF was abolished by ANA-12 (a specific TrkB antagonist) and by K252a (a general Trk antagonist). Astrocytes only express the BDNF receptor TrkB-truncated isoform 1, TrkB-T1. BDNF induced ERK, Akt, and Src (a non-receptor tyrosine kinase) activation in astrocytes. Blocking ERK and Akt pathways abolished BDNF protection in serum deprivation-induced cell death. Moreover, BDNF protected astrocytes from death by 3-nitropropionic acid (3-NP), an effect also blocked by ANA-12, K252a, and inhibitors of ERK, calcium, and Src. BDNF reduced reactive oxygen species levels induced in astrocytes by 3-NP and increased xCT expression and glutathione levels...Continue Reading

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Citations

Aug 3, 2018·Journal of Neurochemistry·Barbara Schweitzer, Jörg B Schulz
Feb 4, 2019·Journal of Neuroendocrinology·Delia RamírezMercedes Lasaga
Feb 15, 2019·International Journal of Molecular Sciences·Zhiwen ZhouRyuta Koyama
May 14, 2020·Brain Sciences·Claudio MolinariFrancesca Uberti
Sep 5, 2020·Oxidative Medicine and Cellular Longevity·Xinyu LiBin Ning
Feb 2, 2019·Neurotoxicity Research·Sachchida Nand RaiSurya Pratap Singh
Jul 13, 2019·Frontiers in Pharmacology·Amanda ThomazRafael Roesler
Sep 21, 2018·Frontiers in Cellular Neuroscience·Xingchun GaoXingchun Gou
Mar 12, 2019·Journal of Huntington's Disease·Nicolas ArbezChristopher A Ross
Aug 29, 2020·Neurochemistry International·Juan TuratiMercedes Lasaga

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