Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties
Open accessAbstract
BACKGROUND: The dominant hypothesis about the pathogenesis of Alzheimer's disease (AD) is the "amyloid cascade" concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD. The molecular mechanisms of this effect are not completely clear, we suggested that the drug might serve as the regulator of the expression of the genes involved in the metabolism of Aβ and the pathogenesis of AD. The study was aimed to determine the effects of CEF on mRNA levels of Bace1 (encoding β-secretase BACE1 involved in Aβ production), Mme, Ide, Ece1, Ace2 (encoding enzymes involved in Aβ degradation), Epo (encoding erythropoietin related to endothelial function and clearance of Aβ across the blood brain barrier) in the frontal cortex, hippocampus, striatum, hypothalamus, and amygdala of OXYS and Wistar (control strain) male rats. Starting from the age of 14 weeks, animals received CEF (100 mg/kg/day, i.p., 36 days) or saline. mRNA levels were evaluated with RT-qPCR method. Biochemical parameters of plasma were measured for control of system effects of the treatment. RESULTS: To better understand strain variations studied here, we compared the gene expression between untreated OXYS and Wistar rats. This comparison showed a significant decrease in mRNA levels of Ace2 in the frontal cortex and hypothalamus, and of Actb in the amygdala of untreated OXYS rats. Analysis of potential effects of CEF revealed its novel targets. In the compound-treated OXYS cohort, CEF diminished mRNA levels of Bace1 and Ace2 in the hypothalamus, and Aktb in the frontal cortex. Furthermore, CEF augmented Mme, Ide, and Epo mRNA levels in the amygdala as well as the levels of Ece1 and Aktb in the striatum. Finally, CEF also attenuated the activity of ALT and AST in plasma of OXYS rats. CONCLUSION: Those findings disclosed novel targets for CEF action that might be involved into neuroprotective mechanisms at early, pre-plaque stages of AD-like pathology development.
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?
Ceftriaxone exerts a neuroprotective effect in various neurodegenerative diseases, such as AD, PD, ALS, and HD.
“Subsequent studies have proved that ceftriaxone exerts a neuroprotective effect in various neurodegenerative diseases, such as AD [14], PD [15], amyotrophic lateral sclerosis (ALS) [16], and Huntington's disease (HD) [17].”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [14]
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
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data
Ruijter, J. M., Ramakers, C., Hoogaars, W. M. H., Karlen, Y., Bakker, O., van den Hoff, M. J. B., & Moorman, A. F. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp045 · Cited by 3,043 · see citing works
Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · see citing works
Sheldon, A. L., & Robinson, M. B. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.03.012 · Cited by 593 · see citing works
β-Actin specifically controls cell growth, migration, and the G-actin pool
Bunnell, T. M., Burbach, B. J., Shimizu, Y., & Ervasti, J. M. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-06-0582 · Cited by 327 · see citing works
Angiotensin‐converting enzyme 2 in the brain: properties and future directions
Xia, H., & Lazartigues, E. D. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05723.x · Cited by 321 · see citing works
Lee, S., Su, Z. Z., Emdad, L., Gupta, P., Sarkar, D., Borjabad, A., Volsky, D. J., & Fisher, P. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707697200 · Cited by 318 · see citing works
Games Played by Rogue Proteins in Prion Disorders and Alzheimer's Disease
Aguzzi, A., & Haass, C. (2003) · Science · doi:10.1126/science.1087348 · Cited by 225 · see citing works
Kehoe, P. G., Wong, S., AL Mulhim, N., Palmer, L. E., & Miners, J. S. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0217-7 · Cited by 203 · see citing works
Singh, S. K., Srivastav, S., Yadav, A. K., Srikrishna, S., & Perry, G. L. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7361613 · Cited by 188 · see citing works
β ‐Amyloid Degradation and Alzheimer′s Disease
Wang, D.-S., Dickson, D. W., & Malter, J. S. (2006) · BioMed Research International · doi:10.1155/jbb/2006/58406 · Cited by 185 · see citing works
Are amyloid‐degrading enzymes viable therapeutic targets in Alzheimer’s disease?
Nalivaeva, N., Beckett, C. S., Belyaev, N. D., & Turner, A. J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07510.x · Cited by 178 · see citing works
Self-citationLewerenz, 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
Grimm, M. O. W., Mett, J., Stahlmann, C. P., Haupenthal, V. J., Zimmer, V. C., & Hartmann, T. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00098 · Cited by 159 · see citing works
Hefendehl, J. K., LeDue, J. M., Ko, R. W. Y., Mahler, J., Murphy, T. H., & MacVicar, B. A. (2016) · Nature Communications · doi:10.1038/ncomms13441 · Cited by 157 · see citing works
Zumkehr, J., Rodríguez‐Ortiz, C. J., Cheng, D., Kieu, Z., Wai, T., Hawkins, C., Kilian, J., Lim, S., Medeiros, R., & Kitazawa, M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.005 · Cited by 152 · see citing works
Zou, K., Yamaguchi, H., Akatsu, H., Sakamoto, T., Ko, M., Mizoguchi, K., Gong, J., Yu, W., Yamamoto, T., Kosaka, K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1549-07.2007 · Cited by 147 · see citing works
Wang, Z., Yang, D., Zhang, X., Li, T., Li, J., Tang, Y., & Le, W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019229 · Cited by 119 · see citing works
Survival and proliferative roles of erythropoietin beyond the erythroid lineage
Noguchi, C. T., Wang, L., Rogers, H. M., Teng, R., & Jia, Y. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000860 · Cited by 113 · see citing works
Stefanova, N. A., Kozhevnikova, O. S., Vitovtov, A. O., Maksimova, K. Y., Logvinov, S. V., Rudnitskaya, E. A., Korbolina, E. E., Muraleva, N. A., & Kolosova, N. G. (2014) · Cell Cycle · doi:10.4161/cc.28255 · Cited by 97 · see citing works
Self-citationLee, S., Chu, K., Park, J., Jung, K., Jeon, D., Lim, J., Lee, S. K., Kim, M., & Roh, J. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07534.x · Cited by 84 · see citing works
Stefanova, N. A., Muraleva, N. A., Skulachev, V. P., & Kolosova, N. G. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-131034 · Cited by 80 · see citing works
Self-citationStefanova, N. A., Фурсова, А. Ж., & Kolosova, N. G. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091675 · Cited by 78 · see citing works
Self-citationZou, K., Maeda, T., Watanabe, A., Liu, J., Liu, S., Oba, R., Satoh, Y.-I., Komano, H., & Michikawa, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.011437 · Cited by 76 · see citing works
Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease
Rudnitskaya, E. A., Maksimova, K. Y., Muraleva, N. A., Logvinov, S. V., Yanshole, L. V., Kolosova, N. G., & Stefanova, N. A. (2014) · Biogerontology · doi:10.1007/s10522-014-9547-7 · Cited by 72 · see citing works
Self-citationCeftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro
Ruzza, P., Siligardi, G., Hussain, R., Marchiani, A., Islami, M., Bubacco, L., Delogu, G., Fabbri, D., Dettori, M. A., Sechi, M., et al. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn400149k · Cited by 70 · see citing works
Moradi, M., Sivadasan, R., Saal-Bauernschubert, L., Lüningschrör, P., Dombert, B., Rathod, R. J., Dieterich, D. C., Blum, R., & Sendtner, M. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201604117 · Cited by 67 · see citing works
Stefanova, N. A., Muraleva, N. A., Korbolina, E. E., Владимировна, К. Е., Maksimova, K. Y., & Kolosova, N. G. (2014) · Oncotarget · doi:10.18632/oncotarget.2751 · Cited by 66 · see citing works
Self-citationLiu, S., Liu, J., Miura, Y., Tanabe, C., Maeda, T., Terayama, Y., Turner, A. J., Zou, K., & Komano, H. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23404 · Cited by 63 · see citing works
Julian, G. S., de Oliveira, R. W., Perry, J. C., Tufik, S. B., & Chagas, J. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109902 · Cited by 53 · see citing works
Kerridge, C., Kozlova, D. I., Nalivaeva, N. N., & Turner, A. J. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00426 · Cited by 51 · see citing works
Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats
Çevik, B., Solmaz, V., Yiğittürk, G., Çavuşoğlu, T., Peker, G., & Erbaş, O. (2017) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/61044 · Cited by 43 · see citing works
Tikhonova, M. A., Ho, S.-C., Akopyan, A. A., Kolosova, N. G., Weng, J., Meng, W.-Y., Lin, C., Amstislavskaya, T. G., & Ho, Y. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.05.002 · Cited by 42 · see citing works
Self-citationRasero, J., Alonso-Montes, C., Diez, I. P., Olabarrieta‐Landa, L., Remaki, L., Escudero, I., Goñi, B. M., Bonifazi, P., Fernández, M., Arango‐Lasprilla, J. C., et al. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00215 · Cited by 32 · see citing works
Huang, C.-K., Chang, Y., Amstislavskaya, T. G., Tikhonova, M. A., Lin, C., Hung, C., Lai, T., & Ho, Y. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.08.011 · Cited by 28 · see citing works
Self-citationCai, J., Li, T., Huang, B., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095974 · Cited by 28 · see citing works
Tikhonova, M. A., Yu, C., Kolosova, N. G., Gerlinskaya, L. A., Maslennikova, S. O., Yudina, A. V., Amstislavskaya, T. G., & Ho, Y. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.01.012 · Cited by 27 · see citing works
Self-citationFu, X., Lin, R., Qiu, Y., Yu, P., & Lei, B. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-21546 · Cited by 26 · see citing works
Агафонова, И. Г., Kolosova, N. G., Mishchenko, N. P., et al. (2007) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-007-0158-z · Cited by 24 · see citing works
Self-citationЛоскутова, Л. В., & Kolosova, N. G. (2000) · Bulletin of Experimental Biology and Medicine · doi:10.1007/bf02766083 · Cited by 23 · see citing works
Self-citationWalder, R. Y., Wattiez, A., White, S. R., et al. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-55 · Cited by 22 · see citing works
Ruzza, P., Vitale, R. M., Hussain, R., Biondi, B., Amodeo, P., Sechi, G., & Siligardi, G. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.04.021 · Cited by 21 · see citing works
New Insights into Epigenetic and Pharmacological Regulation of Amyloid-Degrading Enzymes
Nalivaeva, N. N., Belyaev, N. D., & Turner, A. J. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1703-1 · Cited by 20 · see citing works
Self-citationАгафонова, И. Г., Kotelnikov, V. N., Mischenko, N. P., et al. (2011) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-011-1238-7 · Cited by 17 · see citing works
Retzlaff, C. L., Kussrow, A. K., Schorkopf, T., Saetear, P., Bornhop, D. J., Hardaway, J. A., Sturgeon, S. M., Wright, J., & Blakely, R. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00232 · Cited by 14 · see citing works
Age-Specific Peculiarities of Formation of Long-Term Posttetanic Potentiation in OXYS Rats
Beregovoy, N. A., Sorokina, N., Starostina, M. V., et al. (2011) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-011-1262-7 · Cited by 10 · see citing works
[MORPHOLOGICAL CHARACTERIZATION OF OXYS AND WISTAR RAT HIPPOCAMPUS IN THE AGING PROCESS].
Ky, M., Sv, L., & Stefanova, N. A. (2015) · PubMed · Cited by 4 · see citing works
Stefanova, N. A., Korbolina, E. E., Ershov, N., Rogaev, E. I., & Kolosova, N. G. (2016) · Russian Journal of Genetics Applied Research · doi:10.1134/s2079059716040195 · Cited by 4 · see citing works
Self-citationStefanova, N. A., Korbolina, E. E., Ershov, N., et al. (2015) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vj15.059 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Zhou, X., Lu, J., Wei, K., Wei, J., Tian, P., Yue, M., Wang, Y., Hong, D., Li, F., Wang, B., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9424582 · Cited by 85 · 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
Tai, C.-H., Bellesi, M., Chen, A.-C., Lin, C.-L., Li, H.-H., Lin, P.-J., Liao, W.-C., Hung, C.-S., Schwarting, R. K., & Ho, Y.-J. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.020 · Cited by 34 · see citing works
- Authors
- Tikhonova, M. A., Amstislavskaya, T. G., Belichenko, V. M., Fedoseeva, L. A., Kovalenko, S. P., Pisareva, E. E., Avdeeva, A. S., Kolosova, N. G., Belyaev, N. D., & Aftanas, L. I.
- Affiliations
- Novosibirsk State University (RU)
- Institute of Physiology and Basic Medicine (RU)
- Institute of Cytology and Genetics (RU)
- University of Leeds (GB)
- Corresponding author
- Tikhonova, Maria A.
- ORCID
- Venue
- BMC Neuroscience
- Published
- 2018-04
- Volume
- 19
- Issue
- S1
- Pages
- 13-13
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC5998892
- OpenAlex
- W2801633050
- Cited by
- 30
- References
- 51
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Russian Foundation for Basic Research (0538-2014-0009, 15-04-05593-a)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- ceftriaxone, Alzheimer's disease, amyloid-beta metabolism, neuroprotection, gene expression, BACE1, ACE2, MME, ide, endothelin-converting enzyme-1, erythropoietin, blood-brain barrier, OXYS rats, frontal cortex, hippocampus, amygdala, striatum, hypothalamus
- MeSH terms
- Alzheimer Disease, Animals, Brain, Ceftriaxone, Disease Models, Animal, Male, RNA, Messenger, Gene Expression, Amyloid beta-Peptides, Rats, Wistar, Neuroprotective Agents
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
