Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats
Open accessAbstract
Autophagy maintains cellular homeostasis by stimulating the lysosomal degradation of cytoplasmic structures, including damaged organelles and dysfunctional proteins. The role of autophagy in the renewal and regeneration of injured peripheral nerves remains poorly understood. The current study investigated the role of autophagy in peripheral nerve regeneration and motor function recovery following sciatic nerve crush injury in rats by stimulating or suppressing autophagy and detecting the presence of autophagosomes and LC3-II expression by electron microscopy and Western blotting, respectively. Neurobehavioral function was tested by CatWalk gait analysis 1, 2, 3, and 6 weeks after injury, and the expression of neurofilament (NF)-200 and myelin basic protein (MBP) at the injury site was examined by immunocytochemistry. Apoptosis at the lesion site was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Treatment of injured rats with the autophagy inducer rapamycin increased the number of autophagosomes and LC3-II expression while reducing the number of apoptotic cells at the lesion; this was associated with an upregulation of MBP and NF-200 expression and increased motor function recovery as compared to sham-operated rats and those that were subjected to crush injury but untreated. The opposite effects were observed in rats treated with the autophagy inhibitor 3-methyladenine. These data indicate that the modulation of autophagy in peripheral nerve injury could be an effective pharmacological approach to promote nerve regeneration and reestablish motor function.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration.
“Conversely, stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration [465,466].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [465]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,467 · see citing works
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Laplante, M., & Sabatini, D. (2009) · Journal of Cell Science · doi:10.1242/jcs.051011 · Cited by 2,317 · see citing works
The cellular and molecular basis of peripheral nerve regeneration
Fu, S. Y., & Gordon, T. (1997) · Molecular Neurobiology · doi:10.1007/bf02740621 · Cited by 1,203 · see citing works
Chen, Z., Yu, W., & Strickland, S. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094337 · Cited by 765 · see citing works
Methods for Monitoring Autophagy from Yeast to Human
Klionsky, D. J., Cuervo, A. M., & Seglen, P. O. (2007) · Autophagy · doi:10.4161/auto.3678 · Cited by 656 · see citing works
Autophagy in Human Health and Disease
Doria, A., Gatto, M., & Punzi, L. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1303158 · Cited by 621 · see citing works
Regulation of macroautophagy by mTOR and Beclin 1 complexes
Pattingre, S., Espert, L., Biard‐Piechaczyk, M., & Codogno, P. (2007) · Biochimie · doi:10.1016/j.biochi.2007.08.014 · Cited by 521 · see citing works
Protective role of autophagy in neonatal hypoxia–ischemia induced brain injury
Carloni, S., Buonocore, G., & Balduini, W. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.07.022 · Cited by 444 · see citing works
mTOR and autophagy: a dynamic relationship governed by nutrients and energy.
Dunlop, E., & Tee, A. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.08.006 · Cited by 428 · see citing works
Wen, Y.-D., Sheng, R., Zhang, L.-S., Han, R., Zhang, X., Zhang, X., Han, F., Fukunaga, K., & Qin, Z.-H. (2008) · Autophagy · doi:10.4161/auto.6412 · Cited by 390 · see citing works
Jiang, M., Liu, K., Luo, J., & Dong, Z. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090594 · Cited by 375 · see citing works
Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death
Rami, A., Langhagen, A., & Steiger, S. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.08.005 · Cited by 298 · see citing works
A role for Schwann cell–derived neuregulin-1 in remyelination
Stassart, R. M., Fledrich, R., Velanac, V., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3281 · Cited by 291 · see citing works
Carloni, S., Girelli, S., Scopa, C., Buonocore, G., Longini, M., & Balduini, W. (2010) · Autophagy · doi:10.4161/auto.6.3.11261 · Cited by 269 · see citing works
Molecular mechanisms regulating myelination in the peripheral nervous system
Pereira, J. A., Lebrun-Julien, F., & Suter, U. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.006 · Cited by 253 · see citing works
Sheng, R., Zhang, L., Han, R., Liu, X.-Q., Gao, B., & Qin, Z. (2010) · Autophagy · doi:10.4161/auto.6.4.11737 · Cited by 237 · see citing works
Sekiguchi, A., Kanno, H., Ozawa, H., Yamaya, S., & Itoi, E. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.1919 · Cited by 200 · see citing works
Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration
Madduri, S., & Gander, B. (2010) · Journal of the peripheral nervous system · doi:10.1111/j.1529-8027.2010.00257.x · Cited by 182 · see citing works
The making of successful axonal regeneration: Genes, molecules and signal transduction pathways
Raivich, G., & Makwana, M. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.09.005 · Cited by 168 · see citing works
Chapter 2 Methods for Monitoring Autophagy Using GFP‐LC3 Transgenic Mice
Mizushima, N. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)03602-1 · Cited by 160 · see citing works
Clark, R. S. B., Bayir, H., Chu, C. T., Alber, S. M., Kochanek, P. M., & Watkins, S. C. (2008) · Autophagy · doi:10.4161/auto.5173 · Cited by 148 · see citing works
Moore, M. N. (2008) · Autophagy · doi:10.4161/auto.5528 · Cited by 147 · see citing works
Schwann cell autophagy counteracts the onset and chronification of neuropathic pain
Marinelli, S., Nazio, F., Tinari, A., Ciarlo, L., D'Amelio, M., Pieroni, L., Vacca, V., Urbani, A., Cecconi, F., Malorni, W., et al. (2014) · Pain · doi:10.1016/j.pain.2013.09.013 · Cited by 119 · see citing works
Chen, H.-C., Fong, T.-H., Hsu, P., & Chiu, W. (2012) · Journal of Surgical Research · doi:10.1016/j.jss.2012.02.023 · Cited by 106 · see citing works
Role of Autophagy in Early Brain Injury after Experimental Subarachnoid Hemorrhage
Wang, Z., Shi, X.-Y., Yin, J., Zuo, G., Zhang, J., & Chen, G. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9575-6 · Cited by 105 · see citing works
Autophagy in hypoxia-ischemia induced brain injury
Balduini, W., Carloni, S., & Buonocore, G. (2012) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2012.663176 · Cited by 99 · see citing works
Role of mTOR in neuroprotection and axon regeneration after inflammatory stimulation
Leibinger, M., Andreadaki, A., & Fischer, D. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.01.004 · Cited by 89 · see citing works
Carloni, S., Albertini, M. C., Galluzzi, L., Buonocore, G., Proietti, F., & Balduini, W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.03.002 · Cited by 85 · see citing works
Autophagy and Cell Death: No Longer at Odds
Bergmann, A. (2007) · Cell · doi:10.1016/j.cell.2007.11.027 · Cited by 84 · see citing works
Quercetin alleviates high glucose-induced Schwann cell damage by autophagy
Qu, L., Liang, X., Bei, G., & Liu, W. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.135328 · Cited by 82 · see citing works
Imaging of peripheral nerve lesions
Koltzenburg, M., & Bendszus, M. (2004) · Current Opinion in Neurology · doi:10.1097/00019052-200410000-00013 · Cited by 72 · see citing works
Maeda, H., Nagai, H., Takemura, G., Shintani‐Ishida, K., Komatsu, M., Ogura, S., Aki, T., Shirai, M., Kuwahira, I., & Yoshida, K.-I. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.02.014 · Cited by 62 · see citing works
The protective roles of autophagy in ischemic preconditioning
Yan, W., Dong, H., & Xiong, L. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.18 · Cited by 59 · see citing works
Forghani, R., Garofalo, L., Foran, D. R., Farhadi, H. F., Lepage, P., Hudson, T. J., Tretjakoff, I., Valera, P. B., & Peterson, A. C. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-11-03780.2001 · Cited by 58 · see citing works
Sta, M., Cappaert, N. L. M., Ramekers, D., et al. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.11.012 · Cited by 57 · see citing works
Lu, Y., Wang, W., Song, Y.-Z., et al. (2014) · Pharmaceutical Biology · doi:10.3109/13880209.2014.890232 · Cited by 49 · see citing works
Neuroprotective Effects of Autophagy Induced by Rapamycin in Rat Acute Spinal Cord Injury Model
Wang, Z., Liu, W., Muharram, A., Wu, Z.-Y., & Lin, J. (2014) · NeuroImmunoModulation · doi:10.1159/000357382 · Cited by 47 · see citing works
Kosacka, J., Nowicki, M., Blüher, M., Baum, P., Stockinger, M., Toyka, K. V., Klöting, I., Stümvoll, M., Serke, H., Bechmann, I., et al. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.09.017 · Cited by 39 · see citing works
Xue, Z., Zhang, S., Huang, L., He, Y., Fang, R., & Fang, Y. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-9974-y · Cited by 31 · see citing works
Morphological and functional aspects of sciatic nerve regeneration after crush injury.
Răducan, A., Mirică, S. N., Duicu, O., et al. (2013) · PubMed · Cited by 31 · see citing works
Acute spinal cord injury in rats should target activated autophagy
Hou, H., Zhang, L., Zhang, L., & Tang, P. (2014) · Journal of Neurosurgery Spine · doi:10.3171/2014.1.spine13237 · Cited by 29 · see citing works
Imaging of Peripheral Nerve Lesions
Fahr, L. M., & Sauser, D. D. (1988) · Orthopedic Clinics of North America · doi:10.1016/s0030-5898(20)30328-x · Cited by 15 · see citing works
Psychopharmacological properties of saponins fromRandia niloticastem bark
DANJUMA, N. M., Chindo, B. A., Abdu‐Aguye, I., et al. (2013) · Pharmaceutical Biology · doi:10.3109/13880209.2013.784343 · Cited by 12 · see citing works
Bedi, S. S., Hetz, R. A., Olsen, A. B., Williams, S., Thomas, C. T., Smith, P., Hamilton, J. A., Mays, R. W., & Cox, C. S. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2012.10.358 · Cited by 4 · see citing works
Liu, X., Zhao, M., Mi, J., et al. (2014) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2014.06.007 · Cited by 4 · see citing works
[Autophagy and its role in protective and damaging inflammatory response].
Krejsek, J., Lucia, H., Holmannová, D., et al. (2012) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationAutophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“Conversely, stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration [465,466].”
Background
- Authors
- Huang, H.-C., Chen, L., Zhang, H.-X., Li, S.-F., Liu, P., Zhao, T.-Y., & Li, C.-X.
- Affiliations
- Third Affiliated Hospital of Southern Medical University (CN)
- Corresponding author
- Li, Chuan-xiang
- Venue
- Journal of Molecular Neuroscience
- Published
- 2016-01-07
- Volume
- 58
- Issue
- 4
- Pages
- 416-423
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- PMC
- PMC4829621
- OpenAlex
- W2225840409
- Cited by
- 80
- References
- 52
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 14 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 3 · 2016: 1
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Molecular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Southern Medical University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- autophagy, peripheral nerve regeneration, sciatic nerve crush injury, motor recovery, rapamycin, 3-methyladenine, LC3-II, autophagosomes, apoptosis, myelin basic protein, neurofilaments, gait analysis, peripheral nerve injury
- MeSH terms
- Animals, Autophagy, Myelin Basic Protein, Female, Microtubule-Associated Proteins, Movement, Nerve Regeneration, Sciatic Nerve, Neurofilament Proteins, Rats, Sprague-Dawley, Apoptosis, Rats, Peripheral Nerve Injuries
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review