 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, May 26, 2004, 24(21):5016-5021; doi:10.1523/JNEUROSCI.0820-04.2004
Previous Article | Next Article
Development/Plasticity/Repair
Absence of Glial Fibrillary Acidic Protein and Vimentin Prevents Hypertrophy of Astrocytic Processes and Improves Post-Traumatic Regeneration
Ulrika Wilhelmsson,1 Lizhen Li,1 Marcela Pekna,1 Claes-Henric Berthold,2 Sofia Blom,1 Camilla Eliasson,1 Oliver Renner,5 Eric Bushong,4 Mark Ellisman,4 Todd E. Morgan,3 andMilos Pekny1 1Department of Medical Biochemistry and 2Department of Anatomy and Cell Biology, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden, 3Andrus Gerontology Center, University of Southern California, Los Angeles, California 90089-0191, 4National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, California 92093-0608, and 5Spanish National Cancer Centre, E-28029 Madrid, Spain
The regenerative capacity of the CNS is extremely limited. The reason for this is unclear, but glial cell involvement has been suspected, and oligodendrocytes have been implicated as inhibitors of neuroregeneration (Chen et al., 2000, GrandPre et al., 2000; Fournier et al., 2001). The role of astrocytes in this process was proposed but remains incompletely understood (Silver and Miller, 2004). Astrocyte activation (reactive gliosis) accompanies neurotrauma, stroke, neurodegenerative diseases, or tumors. Two prominent hallmarks of reactive gliosis are hypertrophy of astrocytic processes and upregulation of intermediate filaments. Using the entorhinal cortex lesion model in mice, we found that reactive astrocytes devoid of the intermediate filament proteins glial fibrillary acidic protein and vimentin (GFAP-/-Vim-/-), and consequently lacking intermediate filaments (Colucci-Guyon et al., 1994; Pekny et al., 1995; Eliasson et al., 1999), showed only a limited hypertrophy of cell processes. Instead, many processes were shorter and not straight, albeit the volume of neuropil reached by a single astrocyte was the same as in wild-type mice. This was accompanied by remarkable synaptic regeneration in the hippocampus. On a molecular level, GFAP-/-Vim-/- reactive astrocytes could not upregulate endothelin B receptors, suggesting that the upregulation is intermediate filament dependent. These findings show a novel role for intermediate filaments in astrocytes and implicate reactive astrocytes as potent inhibitors of neuroregeneration.
Key words: GFAP; vimentin; intermediate filaments; astrocytes; regeneration; hippocampus; endothelin B receptor
Received Sep 18, 2003; revised April 8, 2004; accepted April 14, 2004.
This article has been cited by other articles:
M.-D. Perng, S.-F. Wen, T. Gibbon, J. Middeldorp, J. Sluijs, E. M. Hol, and R. A. Quinlan
Glial Fibrillary Acidic Protein Filaments Can Tolerate the Incorporation of Assembly-compromised GFAP-{delta}, but with Consequences for Filament Organization and {alpha}B-Crystallin Association
Mol. Biol. Cell, October 1, 2008; 19(10): 4521 - 4533.
[Abstract] [Full Text] [PDF]
M. R. Verardo, G. P. Lewis, M. Takeda, K. A. Linberg, J. Byun, G. Luna, U. Wilhelmsson, M. Pekny, D.-F. Chen, and S. K. Fisher
Abnormal Reactivity of Muller Cells after Retinal Detachment in Mice Deficient in GFAP and Vimentin
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3659 - 3665.
[Abstract] [Full Text] [PDF]
J. E. Herrmann, T. Imura, B. Song, J. Qi, Y. Ao, T. K. Nguyen, R. A. Korsak, K. Takeda, S. Akira, and M. V. Sofroniew
STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury
J. Neurosci., July 9, 2008; 28(28): 7231 - 7243.
[Abstract] [Full Text] [PDF]
S. Y. Shim, B. A. Samuels, J. Wang, G. Neumayer, C. Belzil, R. Ayala, Y. Shi, Y. Shi, L.-H. Tsai, and M. D. Nguyen
Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth
J. Biol. Chem., May 2, 2008; 283(18): 12232 - 12240.
[Abstract] [Full Text] [PDF]
M. Iribarne, L. Ogawa, V. Torbidoni, C. M. Dodds, R. A. Dodds, and A. M. Suburo
Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice
Am. J. Pathol., April 1, 2008; 172(4): 1030 - 1042.
[Abstract] [Full Text] [PDF]
G. D. King, A.K.M. G. Muhammad, J. F. Curtin, C. Barcia, M. Puntel, C. Liu, S. B. Honig, M. Candolfi, S. Mondkar, P. R. Lowenstein, et al.
Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma model
Neuro-oncol, February 1, 2008; 10(1): 19 - 31.
[Abstract] [Full Text] [PDF]
A. Widestrand, J. Faijerson, U. Wilhelmsson, P. L. P. Smith, L. Li, C. Sihlbom, P. S. Eriksson, and M. Pekny
Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of GFAP / Vim / Mice
Stem Cells, October 1, 2007; 25(10): 2619 - 2627.
[Abstract] [Full Text] [PDF]
T. Nakazawa, M. Takeda, G. P. Lewis, K.-S. Cho, J. Jiao, U. Wilhelmsson, S. K. Fisher, M. Pekny, D. F. Chen, and J. W. Miller
Attenuated Glial Reactions and Photoreceptor Degeneration after Retinal Detachment in Mice Deficient in Glial Fibrillary Acidic Protein and Vimentin
Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2760 - 2768.
[Abstract] [Full Text] [PDF]
R. Jing, U. Wilhelmsson, W. Goodwill, L. Li, Y. Pan, M. Pekny, and O. Skalli
Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks
J. Cell Sci., April 1, 2007; 120(7): 1267 - 1277.
[Abstract] [Full Text] [PDF]
U. Wilhelmsson, E. A. Bushong, D. L. Price, B. L. Smarr, V. Phung, M. Terada, M. H. Ellisman, and M. Pekny
Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury
PNAS, November 14, 2006; 103(46): 17513 - 17518.
[Abstract] [Full Text] [PDF]
H. Li, Y. Guo, J. Teng, M. Ding, A. C. H. Yu, and J. Chen
14-3-3{gamma} affects dynamics and integrity of glial filaments by binding to phosphorylated GFAP
J. Cell Sci., November 1, 2006; 119(21): 4452 - 4461.
[Abstract] [Full Text] [PDF]
J. Nygren, T. Wieloch, J. Pesic, P. Brundin, and T. Deierborg
Enriched Environment Attenuates Cell Genesis in Subventricular Zone After Focal Ischemia in Mice and Decreases Migration of Newborn Cells to the Striatum
Stroke, November 1, 2006; 37(11): 2824 - 2829.
[Abstract] [Full Text] [PDF]
T. L. Hagemann, J. X. Connor, and A. Messing
Alexander Disease-Associated Glial Fibrillary Acidic Protein Mutations in Mice Induce Rosenthal Fiber Formation and a White Matter Stress Response
J. Neurosci., October 25, 2006; 26(43): 11162 - 11173.
[Abstract] [Full Text] [PDF]
M. V. Sofroniew
Reactive Astrocytes in Neural Repair and Protection
Neuroscientist, October 1, 2005; 11(5): 400 - 407.
[Abstract] [PDF]
K.-S. Cho, L. Yang, B. Lu, H. Feng Ma, X. Huang, M. Pekny, and D. F. Chen
Re-establishing the regenerative potential of central nervous system axons in postnatal mice
J. Cell Sci., March 1, 2005; 118(5): 863 - 872.
[Abstract] [Full Text] [PDF]
Y. Goldshmit, M. P. Galea, G. Wise, P. F. Bartlett, and A. M. Turnley
Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice
J. Neurosci., November 10, 2004; 24(45): 10064 - 10073.
[Abstract] [Full Text] [PDF]
D. N. Bowser and B. S. Khakh
ATP Excites Interneurons and Astrocytes to Increase Synaptic Inhibition in Neuronal Networks
J. Neurosci., September 29, 2004; 24(39): 8606 - 8620.
[Abstract] [Full Text] [PDF]
A. Lundkvist, A. Reichenbach, C. Betsholtz, P. Carmeliet, H. Wolburg, and M. Pekny
Under stress, the absence of intermediate filaments from Muller cells in the retina has structural and functional consequences
J. Cell Sci., July 15, 2004; 117(16): 3481 - 3488.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|