Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation
Abnormal phosphorylation and aggregation of tau is a key hallmark of Alzheimer's disease (AD). AD is a multifactorial neurodegenerative disorder for which Diabetes Mellitus (DM) is a risk factor. In animal models for DM, the phosphorylation and aggregation of tau is induced or exacerbated, howe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00432/full |
| _version_ | 1818407463772225536 |
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| author | Judith M Van Der Harg Judith M Van Der Harg Leslie eEggels Silvie R Ruigrok Jeroen JM Hoozemans Susanne E la Fleur Wiep eScheper Wiep eScheper Wiep eScheper |
| author_facet | Judith M Van Der Harg Judith M Van Der Harg Leslie eEggels Silvie R Ruigrok Jeroen JM Hoozemans Susanne E la Fleur Wiep eScheper Wiep eScheper Wiep eScheper |
| author_sort | Judith M Van Der Harg |
| collection | DOAJ |
| description | Abnormal phosphorylation and aggregation of tau is a key hallmark of Alzheimer's disease (AD). AD is a multifactorial neurodegenerative disorder for which Diabetes Mellitus (DM) is a risk factor. In animal models for DM, the phosphorylation and aggregation of tau is induced or exacerbated, however the underlying mechanism is unknown. In addition to the metabolic dysfunction, DM is characterized by chronic low-grade inflammation. This was reported to be associated with a neuroinflammatory response in the hypothalamus of DM animal models. Neuroinflammation is also implicated in the development and progression of AD. It is unknown whether DM also induces neuroinflammation in brain areas affected in AD, the cortex and hippocampus. Here we investigated whether neuroinflammation could be the mechanistic trigger to induce tau phosphorylation in the brain of DM animals. Two distinct diabetic animal models were used; rats on free-choice high-fat high-sugar (fcHFHS) diet that are insulin resistant and streptozotocin-treated rats that are insulin deficient. The streptozotocin-treated animals demonstrated increased tau phosphorylation in the brain as expected, whereas the fcHFHS diet fed animals did not. Remarkably, neither of the diabetic animal models showed reactive microglia or increased GFAP and COX-2 levels in the cortex or hippocampus. From this, we conclude: 1. DM does not induce neuroinflammation in brain regions affected in AD, and 2. Neuroinflammation is not a prerequisite for tau phosphorylation. Neuroinflammation is therefore not the mechanism that explains the close connection between DM and AD. |
| first_indexed | 2024-12-14T09:28:14Z |
| format | Article |
| id | doaj.art-068ef56ff2534255b930594cacf0244c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T09:28:14Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-068ef56ff2534255b930594cacf0244c2022-12-21T23:08:08ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2015-11-01910.3389/fnins.2015.00432167835Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylationJudith M Van Der Harg0Judith M Van Der Harg1Leslie eEggels2Silvie R Ruigrok3Jeroen JM Hoozemans4Susanne E la Fleur5Wiep eScheper6Wiep eScheper7Wiep eScheper8Academic Medical Center, University of AmsterdamCenter for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU UniversityAcademic Medical Center, University of AmsterdamCenter for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU UniversityNeuroscience Campus Amsterdam, VU University Medical CenterAcademic Medical Center, University of AmsterdamAcademic Medical Center, University of AmsterdamCenter for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU UniversityVU University Medical CenterAbnormal phosphorylation and aggregation of tau is a key hallmark of Alzheimer's disease (AD). AD is a multifactorial neurodegenerative disorder for which Diabetes Mellitus (DM) is a risk factor. In animal models for DM, the phosphorylation and aggregation of tau is induced or exacerbated, however the underlying mechanism is unknown. In addition to the metabolic dysfunction, DM is characterized by chronic low-grade inflammation. This was reported to be associated with a neuroinflammatory response in the hypothalamus of DM animal models. Neuroinflammation is also implicated in the development and progression of AD. It is unknown whether DM also induces neuroinflammation in brain areas affected in AD, the cortex and hippocampus. Here we investigated whether neuroinflammation could be the mechanistic trigger to induce tau phosphorylation in the brain of DM animals. Two distinct diabetic animal models were used; rats on free-choice high-fat high-sugar (fcHFHS) diet that are insulin resistant and streptozotocin-treated rats that are insulin deficient. The streptozotocin-treated animals demonstrated increased tau phosphorylation in the brain as expected, whereas the fcHFHS diet fed animals did not. Remarkably, neither of the diabetic animal models showed reactive microglia or increased GFAP and COX-2 levels in the cortex or hippocampus. From this, we conclude: 1. DM does not induce neuroinflammation in brain regions affected in AD, and 2. Neuroinflammation is not a prerequisite for tau phosphorylation. Neuroinflammation is therefore not the mechanism that explains the close connection between DM and AD.http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00432/fullDiabetes MellitusHippocampusInflammationAlzheimer's diseaseCortexdiet-induced obesity |
| spellingShingle | Judith M Van Der Harg Judith M Van Der Harg Leslie eEggels Silvie R Ruigrok Jeroen JM Hoozemans Susanne E la Fleur Wiep eScheper Wiep eScheper Wiep eScheper Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation Frontiers in Neuroscience Diabetes Mellitus Hippocampus Inflammation Alzheimer's disease Cortex diet-induced obesity |
| title | Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation |
| title_full | Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation |
| title_fullStr | Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation |
| title_full_unstemmed | Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation |
| title_short | Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation |
| title_sort | neuroinflammation is not a prerequisite for diabetes induced tau phosphorylation |
| topic | Diabetes Mellitus Hippocampus Inflammation Alzheimer's disease Cortex diet-induced obesity |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00432/full |
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