Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation
Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid-β peptide (Aβ) containing plaques and cognitive deficits. The pathophysiology of AD also involves neuroinflammation. Vitamin B1 (thiamin) is indispensable for normal cellular energy metabolism. Thiamin homeostasis...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122001917 |
| _version_ | 1818465916347744256 |
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| author | Kalidas Ramamoorthy Ryan Yoshimura Saleh Al-Juburi Kasin Y. Anandam Rubina Kapadia Amal Alachkar Geoffrey W. Abbott Hamid M. Said |
| author_facet | Kalidas Ramamoorthy Ryan Yoshimura Saleh Al-Juburi Kasin Y. Anandam Rubina Kapadia Amal Alachkar Geoffrey W. Abbott Hamid M. Said |
| author_sort | Kalidas Ramamoorthy |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid-β peptide (Aβ) containing plaques and cognitive deficits. The pathophysiology of AD also involves neuroinflammation. Vitamin B1 (thiamin) is indispensable for normal cellular energy metabolism. Thiamin homeostasis is altered in AD, and its deficiency is known to aggravate AD pathology. Little, however, is known about possible alterations in level of expression of thiamin transporters-1 and -2 (THTR-1 and -2) in the brain of AD, and whether pro-inflammatory cytokines affect thiamin uptake by brain cells. We addressed these issues using brain tissue samples [prefrontal cortex (PFC) and hippocampus (HIP)] from AD patients and from 5XFAD mouse model of AD, together with cultured human neuroblastoma SH-SY5Y cells as model. Our results revealed a significantly lower expression of both THTR-1 and THTR-2 in the PFC and HIP of AD patients and 5XFAD mouse model of AD compared to appropriate normal controls. Further, we found that exposure of the SH-SY5Y cells to pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) led to a significant inhibition in thiamin uptake. Focusing on IL-1β, we found the inhibition in thiamin uptake to be time-dependent and reversible; it was also associated with a substantial reduction in expression of THTR-1 (but not THTR-2) protein and mRNA as well as a decrease in promoter activity of the SLC19A2 gene (which encodes THTR-1). Finally, using transcriptomic analysis, we found that thiamin availability in SH-SY5Y cells caused changes in the expression of genes relevant to AD pathways. These studies demonstrate, for the first time, that thiamin transport physiology/molecular biology parameters are negatively impacted in AD brain and that pro-inflammatory cytokines inhibit thiamin uptake by neuroblastoma cells. The results also support a possible role for thiamin in the pathophysiology of AD. |
| first_indexed | 2024-04-13T20:52:09Z |
| format | Article |
| id | doaj.art-d7dc5ec5f3234460996273612b28fe77 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-13T20:52:09Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d7dc5ec5f3234460996273612b28fe772022-12-22T02:30:28ZengElsevierNeurobiology of Disease1095-953X2022-09-01171105799Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammationKalidas Ramamoorthy0Ryan Yoshimura1Saleh Al-Juburi2Kasin Y. Anandam3Rubina Kapadia4Amal Alachkar5Geoffrey W. Abbott6Hamid M. Said7Departments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of AmericaDepartments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of AmericaDepartments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of AmericaDepartments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of AmericaMedicine, School of Medicine, University of California, Irvine, CA 92697, United States of AmericaDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States of AmericaDepartments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of AmericaDepartments of Physiology & Biophysics, University of California, Irvine, CA 92697, United States of America; Medicine, School of Medicine, University of California, Irvine, CA 92697, United States of America; Department of Veteran Affairs, VA Medical Center, Long Beach, CA 90822, United States of America; Corresponding author at: 825 Health sciences Road, School of Medicine, University of California, Irvine, CA 92697-4560, United States of America.Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid-β peptide (Aβ) containing plaques and cognitive deficits. The pathophysiology of AD also involves neuroinflammation. Vitamin B1 (thiamin) is indispensable for normal cellular energy metabolism. Thiamin homeostasis is altered in AD, and its deficiency is known to aggravate AD pathology. Little, however, is known about possible alterations in level of expression of thiamin transporters-1 and -2 (THTR-1 and -2) in the brain of AD, and whether pro-inflammatory cytokines affect thiamin uptake by brain cells. We addressed these issues using brain tissue samples [prefrontal cortex (PFC) and hippocampus (HIP)] from AD patients and from 5XFAD mouse model of AD, together with cultured human neuroblastoma SH-SY5Y cells as model. Our results revealed a significantly lower expression of both THTR-1 and THTR-2 in the PFC and HIP of AD patients and 5XFAD mouse model of AD compared to appropriate normal controls. Further, we found that exposure of the SH-SY5Y cells to pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) led to a significant inhibition in thiamin uptake. Focusing on IL-1β, we found the inhibition in thiamin uptake to be time-dependent and reversible; it was also associated with a substantial reduction in expression of THTR-1 (but not THTR-2) protein and mRNA as well as a decrease in promoter activity of the SLC19A2 gene (which encodes THTR-1). Finally, using transcriptomic analysis, we found that thiamin availability in SH-SY5Y cells caused changes in the expression of genes relevant to AD pathways. These studies demonstrate, for the first time, that thiamin transport physiology/molecular biology parameters are negatively impacted in AD brain and that pro-inflammatory cytokines inhibit thiamin uptake by neuroblastoma cells. The results also support a possible role for thiamin in the pathophysiology of AD.http://www.sciencedirect.com/science/article/pii/S0969996122001917Alzheimer's diseaseThiamin transporters −1 and −2Pro-inflammatory cytokinesThiamin uptake |
| spellingShingle | Kalidas Ramamoorthy Ryan Yoshimura Saleh Al-Juburi Kasin Y. Anandam Rubina Kapadia Amal Alachkar Geoffrey W. Abbott Hamid M. Said Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation Neurobiology of Disease Alzheimer's disease Thiamin transporters −1 and −2 Pro-inflammatory cytokines Thiamin uptake |
| title | Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation |
| title_full | Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation |
| title_fullStr | Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation |
| title_full_unstemmed | Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation |
| title_short | Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation |
| title_sort | alzheimer s disease is associated with disruption in thiamin transport physiology a potential role for neuroinflammation |
| topic | Alzheimer's disease Thiamin transporters −1 and −2 Pro-inflammatory cytokines Thiamin uptake |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122001917 |
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