Truncated TrkB.T1-mediated astrocyte dysfunction contributes to impaired motor function and neuropathic pain after spinal cord injury
JournalJournal of Neuroscience
PublisherSociety for Neuroscience
MetadataShow full item record
AbstractFollowing spinal cord injury (SCI), astrocytes demonstrate long-lasting reactive changes, which are associated with the persistence of neuropathic pain and motor dysfunction. We previously demonstrated that upregulation of trkB.T1, a truncated isoform of the brainderived neurotrophic factor receptor (BDNF), contributes to gliosis after SCI, but little is known about the effects of trkB.T1 on the function of astrocytes. As trkB.T1 is the sole isoform of trkB receptors expressed on astrocytes, we examined the function of trkB.T1- driven astrocytes in vitro and in vivo. Immunohistochemistry showed that trkB.T1+ cells were significantly upregulated 7 d after injury, with sustained elevation in white matter through 8 weeks. The latter increase was predominantly found in astrocytes. TrkB.T1 was also highly expressed by neurons and microglia/macrophages at 7 d after injury and declined by 8 weeks. RNA sequencing of cultured astrocytes derived from trkB.T1+/+(WT) and trkB.T1-/-(KO) mice revealed downregulation of migration and proliferation pathways in KO astrocytes. KO astrocytes also exhibited slower migration/proliferation in vitro in response to FBS or BDNF compared with WT astrocytes. Reduced proliferation of astrocytes was also confirmed after SCI in astrocyte-specific trkB.T1 KO mice; using mechanical allodynia and pain-related measurements on the CatWalk, these animals also showed reduced hyperpathic responses, along with improved motor coordination. Together, our data indicate that trkB.T1 in astrocytes contributes to neuropathic pain and neurological dysfunction following SCI, suggesting that trkB.T1 may provide a novel therapeutic target for SCI. Copyright 2017 the authors.
SponsorsThis work was supported by grants from National Institutes of Health(R01 NR013601,NIH T32 HL007698.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85019054293&doi=10.1523%2fJNEUROSCI.3353-16.2017&partnerID=40&md5=de0f84e203f2c80706ebacb48bff45d4; http://hdl.handle.net/10713/10044
- TrkB.T1 contributes to neuropathic pain after spinal cord injury through regulation of cell cycle pathways.
- Authors: Wu J, Renn CL, Faden AI, Dorsey SG
- Issue date: 2013 Jul 24
- Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain.
- Authors: Cao T, Matyas JJ, Renn CL, Faden AI, Dorsey SG, Wu J
- Issue date: 2020 May 11
- Intermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal brain-derived neurotrophic factor-tropomyosin-receptor kinase signaling in adult rats.
- Authors: Garraway SM, Turtle JD, Huie JR, Lee KH, Hook MA, Woller SA, Grau JW
- Issue date: 2011 Dec 29
- Down-regulation of zinc transporter-1 in astrocytes induces neuropathic pain via the brain-derived neurotrophic factor - K<sup>+</sup>-Cl<sup>-</sup> co-transporter-2 signaling pathway in the mouse spinal cord.
- Authors: Kitayama T, Morita K, Motoyama N, Dohi T
- Issue date: 2016 Dec
- Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation.
- Authors: Geng SJ, Liao FF, Dang WH, Ding X, Liu XD, Cai J, Han JS, Wan Y, Xing GG
- Issue date: 2010 Apr