Alterations in Neuronal Survival and Glial Reactions after Axotomy by Ceftriaxone and Minocycline in the Mouse Hypoglossal Nucleus
Abstract
Some antibiotics are suggested to exert neuroprotective effects via regulation of glial responses. Attenuation of microglial activation by minocycline prevents neuronal death in a variety of experimental models for neurological diseases, such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1). However, it remains largely unknown whether these antibiotics are able to protect neurons in axotomy models for progressive motor neuron diseases. Recent studies have shown that the axotomized motoneurons of the adult rat can survive, whereas those of the adult mouse undergo neuronal degeneration. We thus examined the possible effects of ceftriaxone and minocycline on neuronal loss and glial reactions in the mouse hypoglossal nucleus after axotomy. The survival rate of lesioned motoneurons at 28 days after axotomy (D28) was significantly improved by ceftriaxone and minocycline treatment. There were no significant differences in the cellular densities of astrocytes between ceftriaxone-treated and saline-treated animals. Ceftriaxone administration increased the expression of GLT-1 in the hypoglossal nucleus, while it suppressed the reactive increase of glial fibrillary acidic protein (GFAP) expression to control level. The cellular densities of microglia at D28 were significantly lower in minocycline-treated mice than in saline-treated mice. The time course analysis showed that immediate increase in microglia at D3 and D7 was not suppressed by minocycline. The present observations show that minocycline and ceftriaxone promote survival of lesioned motoneurons in the mouse hypoglossal nucleus, and also suggest that alterations in glial responses might be involved in neuroprotective actions of antibiotics.
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Treatment of several PD animal models with CTX stimulates neurogenesis.
“The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [225,226,227,228].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [227]
Treatment of several PD animal models with CTX promotes astrocyte viability.
“The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [225,226,227,228].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [227]
Treatment of several PD animal models with CTX improves neuroinflammatory markers.
“The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [225,226,227,228].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [227]
Treatment of several PD animal models with CTX improves oxidative stress markers.
“The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [225,226,227,228].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [227]
CTX suppresses NF-κB/c-Jun-mediated signaling.
“The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [225,226,227,228].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [227]
Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · see citing works
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196 · see citing works
β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
Rothstein, J. D., Patel, S., Regan, M. R., Haenggeli, C., Huang, Y. H., Bergles, D. E., Jin, L., Dykes Hoberg, M., Vidensky, S., Chung, D. S., et al. (2005) · Nature · doi:10.1038/nature03180 · Cited by 1,518 · see citing works
Glia: listening and talking to the synapse
Haydon, P. G. (2001) · Nature reviews. Neuroscience · doi:10.1038/35058528 · Cited by 1,410 · see citing works
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia
Yrjänheikki, J., Keinänen, R., Pellikka, M., Hökfelt, T., & Koistinaho, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15769 · Cited by 1,006 · see citing works
Tikka, T., Fiebich, B. L., Goldsteins, G., Keinänen, R., & Koistinaho, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02580.2001 · Cited by 958 · see citing works
Displacement of synaptic terminals from regenerating motoneurons by microglial cells
Blinzinger, K., & Kreutzberg, G. W. (1968) · Cell and Tissue Research · doi:10.1007/bf00325030 · Cited by 855 · see citing works
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787 · see citing works
Microglia: biology and pathology
Graeber, M., & Streit, W. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0622-0 · Cited by 729 · see citing works
Minocycline and Neurodegenerative Diseases
Kim, H.-S., & Suh, Y.-H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.040 · Cited by 447 · see citing works
Central neuron–glial and glial–glial interactions following axon injury
Aldskogius, H., & Kozlova, E. N. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00093-2 · Cited by 350 · see citing works
Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy
Graeber, M. B., Tetzlaff, W., Streit, W. J., & Kreutzberg, G. W. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90585-x · Cited by 333 · see citing works
Neuroprotection by tetracyclines
Domercq, M., & Matute, C. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.10.001 · Cited by 205 · see citing works
Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation
Chu, K., Lee, S., Sinn, D.-I., Ko, S., Kim, E., Kim, J., Kim, S., Park, D.-K., Jung, K., Song, E., et al. (2006) · Stroke · doi:10.1161/01.str.0000252091.36912.65 · Cited by 188 · see citing works
Delayed astrocyte reaction following facial nerve axotomy
Graeber, M. B., & Kreutzberg, G. W. (1988) · Journal of Neurocytology · doi:10.1007/bf01674208 · Cited by 183 · see citing works
Lewerenz, J., Albrecht, P., Tien, M. T., Henke, N., Karumbayaram, S., Kornblum, H. I., Wiedau‐Pazos, M., Schubert, D., Maher, P. A., & Methner, A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06347.x · Cited by 174 · see citing works
S100 protein expression in subpopulations of neurons of rat brain
Rickmann, M., & Wolff, J. R. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00615-c · Cited by 135 · see citing works
Axotomy abolishes NeuN expression in facial but not rubrospinal neurons
McPhail, L. T., McBride, C. B., McGraw, J., Steeves, J. D., & Tetzlaff, W. (2003) · Experimental Neurology · doi:10.1016/j.expneurol.2003.10.001 · Cited by 103 · see citing works
Lefrançois, T., Fages, C., Peschanski, M., & Tardy, M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-11-04121.1997 · Cited by 80 · see citing works
Axotomy as an Experimental Model of Neuronal Injury and Cell Death
Koliatsos, V. E., & Price, D. L. (1996) · Brain Pathology · doi:10.1111/j.1750-3639.1996.tb00875.x · Cited by 67 · see citing works
Nizzardo, M., Nardini, M., Ronchi, D., Salani, S., Donadoni, C., Fortunato, F., Colciago, G., Falcone, M., Simone, C., Riboldi, G., et al. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.017 · Cited by 64 · see citing works
Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus
McAllister, J. P., & Miller, J. M. (2010) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-7-7 · Cited by 49 · see citing works
Yamada, J., Nakanishi, H., & Jinno, S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.030 · Cited by 45 · see citing works
Bachetti, T., Zanni, E. D., Balbi, P., Bocca, P., Prigione, I., Deiana, G. A., Rezzani, A., Ceccherini, I., & Sechi, G. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.05.005 · Cited by 39 · see citing works
Antibiotics rescue neurons from glutamate attack
Tanaka, K. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.04.002 · Cited by 24 · see citing works
Fendrick, S. E., Miller, K. R., & Streit, W. J. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.05.047 · Cited by 23 · see citing works
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Konishi, H., & Kiyama, H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00206 · Cited by 300 · see citing works
Brites, D. M. T. O. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00088 · Cited by 142 · see citing works
The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury
Pottorf, T. S., Rotterman, T. M., McCallum, W. M., Haley-Johnson, Z., & Álvarez, F. J. (2022) · Cells · doi:10.3390/cells11132083 · Cited by 93 · see citing works
Varesi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012289 · Cited by 88 · see citing works
Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review
Yimer, E. M., Hishe, H. Z., & Tuem, K. B. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00236 · Cited by 72 · see citing works
Smaga, I., Fierro, D., Mesa, J., Filip, M., & Knackstedt, L. A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.05.016 · Cited by 69 · see citing works
Nicholson, K. J., Gilliland, T. M., & Winkelstein, B. A. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23295 · Cited by 58 · see citing works
Yamada, J., & Jinno, S. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23228 · Cited by 58 · see citing works
Ide, M., Sonoda, N., Inoue, T., Kimura, S., Minami, Y., Makimura, H., Hayashida, E., Hyodo, F., Yamato, M., Takayanagi, R., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228750 · Cited by 44 · see citing works
Jinno, S., & Yamada, J. (2011) · Neuron Glia Biology · doi:10.1017/s1740925x11000135 · Cited by 24 · see citing works
Yamada, J., & Jinno, S. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.068 · Cited by 19 · see citing works
Takaso, Y., Noda, M., Hattori, T., Roboon, J., Hatano, M., Sugimoto, H., Brenner, C., Yamamoto, Y., Okamoto, H., Higashida, H., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-73984-3 · Cited by 17 · see citing works
Yang, L., Li, X., Shiquan, W., Chen, Y., Shuzhuo, Z., & Zhang, H. (2014) · International Journal of Neuroscience · doi:10.3109/00207454.2013.856009 · Cited by 16 · see citing works
Ceftriaxone for Alexander’s Disease: A Four-Year Follow-Up
Sechi, G., Ceccherini, I., Bachetti, T., Deiana, G. A., Sechi, E., & Balbi, P. (2012) · JIMD Reports · doi:10.1007/8904_2012_180 · Cited by 14 · see citing works
Hosain, M. Z., Mori, T., Kishimura, A., & Katayama, Y. (2015) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2015.1125565 · Cited by 14 · see citing works
Microglia support ATF3-positive neurons following hypoglossal nerve axotomy
Tanaka, T., Murakami, K., Bando, Y., Nomura, T., Isonishi, A., Morita-Takemura, S., Tatsumi, K., Wanaka, A., & Yoshida, S. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.05.007 · Cited by 13 · see citing works
Schram, S., Loeb, J. A., & Song, F. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01849-7 · Cited by 12 · see citing works
Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?
Rodriguez, P., & Blakely, R. (2023) · Journal of Cellular Physiology · doi:10.1002/jcp.31125 · Cited by 7 · see citing works
Rotterman, T. M., García, V. V., Housley, S. N., Nardelli, P., Sierra, R., Fix, C. E., & Cope, T. C. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0103-23.2023 · Cited by 8 · see citing works
Minocycline and Cephalexin in a Patient with Spastic Neuropathic Pain Secondary to Neurosarcoidosis
Mohan, A., Lefstein, K. M., & Chang, E. (2021) · Pain Medicine · doi:10.1093/pm/pnab044 · Cited by 2 · see citing works
Duque, É. D. A. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2019.tde-15102019-100704
- Authors
- Yamada, J., & Jinno, S.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Jinno, Shozo
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 504
- Issue
- 3
- Pages
- 295-300
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1979678315
- Cited by
- 21
- References
- 26
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- ceftriaxone, minocycline, axotomy, hypoglossal nucleus, motoneuron survival, neuroprotection, microglial activation, astrocytes, GLT-1, glutamate transporters, glial fibrillary acidic protein, glial reaction, motor neuron disease
- MeSH terms
- Animals, Astrocytes, Ceftriaxone, Cell Survival, Disease Models, Animal, Drug Interactions, Drug Evaluation, Preclinical, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Minocycline, Nerve Tissue Proteins, Neurons, Motor Neuron Disease, Microglia, Neuroprotective Agents, Axotomy, Mice, Hypoglossal Nerve Injuries
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