Cargando…
Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease
BACKGROUND: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease affecting many cellular pathways, including protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation. Currently, no effective treatment for AD exists. OBJECTIVE: We aim to determine...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535606/ https://www.ncbi.nlm.nih.gov/pubmed/36275418 http://dx.doi.org/10.3233/ADR-220025 |
_version_ | 1784802808856313856 |
---|---|
author | Lu, Lu-Ping Chang, Wei-Hua Huang, Jing-Jia Tan, Peng Tsai, Guochuan Emil |
author_facet | Lu, Lu-Ping Chang, Wei-Hua Huang, Jing-Jia Tan, Peng Tsai, Guochuan Emil |
author_sort | Lu, Lu-Ping |
collection | PubMed |
description | BACKGROUND: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease affecting many cellular pathways, including protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation. Currently, no effective treatment for AD exists. OBJECTIVE: We aim to determine the effect of lithium benzoate (LiBen) in protecting neurons from amyloid-β (Aβ) or other neurotoxin insults. METHODS: Primary rat cortical neurons co-treated with neurotoxins and LiBen were used to examine its effect in cell viability, reactive oxygen species (ROS) clearance, and mitochondrial functions by MTT, CellRox fluorescence staining, and seahorse assay. Then, Barnes maze and prepulse inhibition test were performed in APP/PS1 mice that received chronic LiBen treatment to assess its effect on cognitive protection. Oral bioavailability of LiBen was also assessed by pharmacokinetic study in rat plasma. RESULTS: In this study, we discovered that LiBen can attenuate cellular ROS level, improve mitochondrial function, increase cell viability against multiple different insults of mitochondrial dysfunction, Aβ accumulation, and neuroinflammation, and promote neurogenesis. We demonstrated that LiBen has advantages over lithium or sodium benzoate alone as LiBen displays superior neuroprotective efficacy and oral bioavailability than the other two agents when being applied either alone or in combination. Furthermore, chronic administration of LiBen showed protection for cognition as well as spatial memory and reduced the senile plaque deposition in brains of AD animal models. CONCLUSION: LiBen stands as a promising therapeutic agent for improving cognition and delaying the progression of AD. |
format | Online Article Text |
id | pubmed-9535606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95356062022-10-20 Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease Lu, Lu-Ping Chang, Wei-Hua Huang, Jing-Jia Tan, Peng Tsai, Guochuan Emil J Alzheimers Dis Rep Research Report BACKGROUND: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease affecting many cellular pathways, including protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation. Currently, no effective treatment for AD exists. OBJECTIVE: We aim to determine the effect of lithium benzoate (LiBen) in protecting neurons from amyloid-β (Aβ) or other neurotoxin insults. METHODS: Primary rat cortical neurons co-treated with neurotoxins and LiBen were used to examine its effect in cell viability, reactive oxygen species (ROS) clearance, and mitochondrial functions by MTT, CellRox fluorescence staining, and seahorse assay. Then, Barnes maze and prepulse inhibition test were performed in APP/PS1 mice that received chronic LiBen treatment to assess its effect on cognitive protection. Oral bioavailability of LiBen was also assessed by pharmacokinetic study in rat plasma. RESULTS: In this study, we discovered that LiBen can attenuate cellular ROS level, improve mitochondrial function, increase cell viability against multiple different insults of mitochondrial dysfunction, Aβ accumulation, and neuroinflammation, and promote neurogenesis. We demonstrated that LiBen has advantages over lithium or sodium benzoate alone as LiBen displays superior neuroprotective efficacy and oral bioavailability than the other two agents when being applied either alone or in combination. Furthermore, chronic administration of LiBen showed protection for cognition as well as spatial memory and reduced the senile plaque deposition in brains of AD animal models. CONCLUSION: LiBen stands as a promising therapeutic agent for improving cognition and delaying the progression of AD. IOS Press 2022-09-20 /pmc/articles/PMC9535606/ /pubmed/36275418 http://dx.doi.org/10.3233/ADR-220025 Text en © 2022 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Lu, Lu-Ping Chang, Wei-Hua Huang, Jing-Jia Tan, Peng Tsai, Guochuan Emil Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title | Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title_full | Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title_fullStr | Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title_full_unstemmed | Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title_short | Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer’s Disease |
title_sort | lithium benzoate exerts neuroprotective effect by improving mitochondrial function, attenuating reactive oxygen species, and protecting cognition and memory in an animal model of alzheimer’s disease |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535606/ https://www.ncbi.nlm.nih.gov/pubmed/36275418 http://dx.doi.org/10.3233/ADR-220025 |
work_keys_str_mv | AT luluping lithiumbenzoateexertsneuroprotectiveeffectbyimprovingmitochondrialfunctionattenuatingreactiveoxygenspeciesandprotectingcognitionandmemoryinananimalmodelofalzheimersdisease AT changweihua lithiumbenzoateexertsneuroprotectiveeffectbyimprovingmitochondrialfunctionattenuatingreactiveoxygenspeciesandprotectingcognitionandmemoryinananimalmodelofalzheimersdisease AT huangjingjia lithiumbenzoateexertsneuroprotectiveeffectbyimprovingmitochondrialfunctionattenuatingreactiveoxygenspeciesandprotectingcognitionandmemoryinananimalmodelofalzheimersdisease AT tanpeng lithiumbenzoateexertsneuroprotectiveeffectbyimprovingmitochondrialfunctionattenuatingreactiveoxygenspeciesandprotectingcognitionandmemoryinananimalmodelofalzheimersdisease AT tsaiguochuanemil lithiumbenzoateexertsneuroprotectiveeffectbyimprovingmitochondrialfunctionattenuatingreactiveoxygenspeciesandprotectingcognitionandmemoryinananimalmodelofalzheimersdisease |