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Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies
Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transpo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543807/ https://www.ncbi.nlm.nih.gov/pubmed/31178684 http://dx.doi.org/10.3389/fnins.2019.00507 |
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author | Ho, Ying-Jui Shen, Mei-Shiuan Tai, Chun-Hwei Li, Hsin-Hua Chen, Jian-Horng Liao, Wen-Chieh Chiu, Pai-Yi Lee, I-Yen Lin, Chih-Li Hung, Ching-Sui |
author_facet | Ho, Ying-Jui Shen, Mei-Shiuan Tai, Chun-Hwei Li, Hsin-Hua Chen, Jian-Horng Liao, Wen-Chieh Chiu, Pai-Yi Lee, I-Yen Lin, Chih-Li Hung, Ching-Sui |
author_sort | Ho, Ying-Jui |
collection | PubMed |
description | Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transporter 1 expression and glutamate reuptake. We investigated whether CEF can prevent cognitive decline and neurological deficits and increase neurogenesis in DLB rats. Male Wistar rats infused with viral vector containing human alpha-synuclein (α-syn) gene, SNCA, in the lateral ventricle were used as a rat model of DLB. CEF (100 mg/kg/day, i.p.) was injected in these rats for 27 days. The active avoidance test and object recognition test was performed. Finally, the brains of all the rats were immunohistochemically stained to measure α-syn, neuronal density, and newborn cells in the hippocampus and substantia nigra. The results revealed that DLB rats had learning and object recognition impairments and exhibited cell loss in the nigrostriatal dopaminergic system, and hippocampal CA1, and dentate gyrus (DG). Additionally, DLB rats had fewer newborn cells in the DG and substantia nigra pars reticulata and more α-syn immune-positive cells in the DG. Treatment with CEF improved cognitive function, reduced cell loss, and increased the number of newborn cells in the brain. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of DLB rats. CEF may therefore has clinical potential for treating DLB. |
format | Online Article Text |
id | pubmed-6543807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65438072019-06-07 Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies Ho, Ying-Jui Shen, Mei-Shiuan Tai, Chun-Hwei Li, Hsin-Hua Chen, Jian-Horng Liao, Wen-Chieh Chiu, Pai-Yi Lee, I-Yen Lin, Chih-Li Hung, Ching-Sui Front Neurosci Neuroscience Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transporter 1 expression and glutamate reuptake. We investigated whether CEF can prevent cognitive decline and neurological deficits and increase neurogenesis in DLB rats. Male Wistar rats infused with viral vector containing human alpha-synuclein (α-syn) gene, SNCA, in the lateral ventricle were used as a rat model of DLB. CEF (100 mg/kg/day, i.p.) was injected in these rats for 27 days. The active avoidance test and object recognition test was performed. Finally, the brains of all the rats were immunohistochemically stained to measure α-syn, neuronal density, and newborn cells in the hippocampus and substantia nigra. The results revealed that DLB rats had learning and object recognition impairments and exhibited cell loss in the nigrostriatal dopaminergic system, and hippocampal CA1, and dentate gyrus (DG). Additionally, DLB rats had fewer newborn cells in the DG and substantia nigra pars reticulata and more α-syn immune-positive cells in the DG. Treatment with CEF improved cognitive function, reduced cell loss, and increased the number of newborn cells in the brain. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of DLB rats. CEF may therefore has clinical potential for treating DLB. Frontiers Media S.A. 2019-05-24 /pmc/articles/PMC6543807/ /pubmed/31178684 http://dx.doi.org/10.3389/fnins.2019.00507 Text en Copyright © 2019 Ho, Shen, Tai, Li, Chen, Liao, Chiu, Lee, Lin and Hung. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Ho, Ying-Jui Shen, Mei-Shiuan Tai, Chun-Hwei Li, Hsin-Hua Chen, Jian-Horng Liao, Wen-Chieh Chiu, Pai-Yi Lee, I-Yen Lin, Chih-Li Hung, Ching-Sui Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title | Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title_full | Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title_fullStr | Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title_full_unstemmed | Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title_short | Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies |
title_sort | use of ceftriaxone in treating cognitive and neuronal deficits associated with dementia with lewy bodies |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543807/ https://www.ncbi.nlm.nih.gov/pubmed/31178684 http://dx.doi.org/10.3389/fnins.2019.00507 |
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