Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease
Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996120300206 |
| _version_ | 1818336646316163072 |
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| author | Divna Lazic Vesna Tesic Mirna Jovanovic Marjana Brkic Desanka Milanovic Berislav V. Zlokovic Selma Kanazir Milka Perovic |
| author_facet | Divna Lazic Vesna Tesic Mirna Jovanovic Marjana Brkic Desanka Milanovic Berislav V. Zlokovic Selma Kanazir Milka Perovic |
| author_sort | Divna Lazic |
| collection | DOAJ |
| description | Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease.EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice.Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease. |
| first_indexed | 2024-12-13T14:42:38Z |
| format | Article |
| id | doaj.art-e57c6f378e7a4cc1b832b4422269acab |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:42:38Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e57c6f378e7a4cc1b832b4422269acab2022-12-21T23:41:34ZengElsevierNeurobiology of Disease1095-953X2020-03-01136104745Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's diseaseDivna Lazic0Vesna Tesic1Mirna Jovanovic2Marjana Brkic3Desanka Milanovic4Berislav V. Zlokovic5Selma Kanazir6Milka Perovic7Department of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, Serbia; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo St, 90033 Los Angeles, CA, USA; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, 1501 San Pablo St, 90033 Los Angeles, CA, USADepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, SerbiaZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo St, 90033 Los Angeles, CA, USA; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, 1501 San Pablo St, 90033 Los Angeles, CA, USADepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research ''Siniša Stanković''- National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11000 Belgrade, Serbia; Corresponding author at: Bulevar despota Stefana 142, 11000 Belgrade, Serbia.Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease.EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice.Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease.http://www.sciencedirect.com/science/article/pii/S0969996120300206Alzheimer's disease5XFADEOD dietary restrictionIntermittent fastingInflammationSynaptic plasticity |
| spellingShingle | Divna Lazic Vesna Tesic Mirna Jovanovic Marjana Brkic Desanka Milanovic Berislav V. Zlokovic Selma Kanazir Milka Perovic Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease Neurobiology of Disease Alzheimer's disease 5XFAD EOD dietary restriction Intermittent fasting Inflammation Synaptic plasticity |
| title | Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease |
| title_full | Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease |
| title_fullStr | Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease |
| title_full_unstemmed | Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease |
| title_short | Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease |
| title_sort | every other day feeding exacerbates inflammation and neuronal deficits in 5xfad mouse model of alzheimer s disease |
| topic | Alzheimer's disease 5XFAD EOD dietary restriction Intermittent fasting Inflammation Synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996120300206 |
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