Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice
Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer’s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to t...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.753351/full |
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| author | Bo-Wen Chen Bo-Wen Chen Bo-Wen Chen Kai-Wen Zhang Kai-Wen Zhang Kai-Wen Zhang Si-Jia Chen Si-Jia Chen Si-Jia Chen Chun Yang Chun Yang Chun Yang Peng-Gao Li Peng-Gao Li Peng-Gao Li |
| author_facet | Bo-Wen Chen Bo-Wen Chen Bo-Wen Chen Kai-Wen Zhang Kai-Wen Zhang Kai-Wen Zhang Si-Jia Chen Si-Jia Chen Si-Jia Chen Chun Yang Chun Yang Chun Yang Peng-Gao Li Peng-Gao Li Peng-Gao Li |
| author_sort | Bo-Wen Chen |
| collection | DOAJ |
| description | Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer’s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL/6J amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-β peptides (Aβ40 and Aβ42) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of Lactobacillus and significantly different α- and β-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism. |
| first_indexed | 2024-12-22T05:18:10Z |
| format | Article |
| id | doaj.art-eac3db6ff8eb472bb2fb2882e86f751a |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T05:18:10Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-eac3db6ff8eb472bb2fb2882e86f751a2022-12-21T18:37:48ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-11-011310.3389/fnagi.2021.753351753351Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic MiceBo-Wen Chen0Bo-Wen Chen1Bo-Wen Chen2Kai-Wen Zhang3Kai-Wen Zhang4Kai-Wen Zhang5Si-Jia Chen6Si-Jia Chen7Si-Jia Chen8Chun Yang9Chun Yang10Chun Yang11Peng-Gao Li12Peng-Gao Li13Peng-Gao Li14School of Public Health, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Environmental Toxicology, Beijing, ChinaBeijing Key Laboratory of Clinical Epidemiology, Beijing, ChinaSchool of Public Health, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Environmental Toxicology, Beijing, ChinaBeijing Key Laboratory of Clinical Epidemiology, Beijing, ChinaSchool of Public Health, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Environmental Toxicology, Beijing, ChinaBeijing Key Laboratory of Clinical Epidemiology, Beijing, ChinaSchool of Public Health, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Environmental Toxicology, Beijing, ChinaBeijing Key Laboratory of Clinical Epidemiology, Beijing, ChinaSchool of Public Health, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Environmental Toxicology, Beijing, ChinaBeijing Key Laboratory of Clinical Epidemiology, Beijing, ChinaVitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer’s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL/6J amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-β peptides (Aβ40 and Aβ42) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of Lactobacillus and significantly different α- and β-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism.https://www.frontiersin.org/articles/10.3389/fnagi.2021.753351/fullvitamin A deficiencyAlzheimer’s diseasegut microbiota dysbiosiscognitive deficitsAPP/PS1 transgenic mice |
| spellingShingle | Bo-Wen Chen Bo-Wen Chen Bo-Wen Chen Kai-Wen Zhang Kai-Wen Zhang Kai-Wen Zhang Si-Jia Chen Si-Jia Chen Si-Jia Chen Chun Yang Chun Yang Chun Yang Peng-Gao Li Peng-Gao Li Peng-Gao Li Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice Frontiers in Aging Neuroscience vitamin A deficiency Alzheimer’s disease gut microbiota dysbiosis cognitive deficits APP/PS1 transgenic mice |
| title | Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice |
| title_full | Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice |
| title_fullStr | Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice |
| title_full_unstemmed | Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice |
| title_short | Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice |
| title_sort | vitamin a deficiency exacerbates gut microbiota dysbiosis and cognitive deficits in amyloid precursor protein presenilin 1 transgenic mice |
| topic | vitamin A deficiency Alzheimer’s disease gut microbiota dysbiosis cognitive deficits APP/PS1 transgenic mice |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.753351/full |
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