High-Fat-Diet-Induced Metabolic Disorders: An Original Cause for Neurovascular Uncoupling Through the Imbalance of Glutamatergic Pathways
<b>Backgrounds/Objective:</b> The impact of metabolic disturbances induced by an unbalanced diet on cognitive decline in mid-life is now widely observed, although the mechanisms are not well identified. Here we report that glutamatergic vasoactive pathways are a key feature of high-fat-d...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1712 |
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| Summary: | <b>Backgrounds/Objective:</b> The impact of metabolic disturbances induced by an unbalanced diet on cognitive decline in mid-life is now widely observed, although the mechanisms are not well identified. Here we report that glutamatergic vasoactive pathways are a key feature of high-fat-diet (HFD)-induced neurogliovascular uncoupling in mice. <b>Methods:</b> C57Bl6/J mice are fed either with normal diet (ND) or high-fat diet (HFD) during 6 or 12 months and characterized for metabolic status. Cerebral vascular tree from pial to intraparenchymal arteries, is investigated with Halpern’s arteriography and with differential interference contrast infrared imaging of brain slices. <b>Results:</b> A 70% alteration in the myogenic tone of the basilar artery is observed as early as 6 months (M6) after the HFD. Infrared imaging revealed a 77% reduction in the glutamate-induced vasodilation of intraparenchymal arterioles appearing after 12 months (M12) of the HFD. The respective contributions of enzymes involved in glutamatergic pathways were altered as a function of HFD and time. The decrease in astrocytic COX I observed at M6 was followed by a loss of neuronal COX II and a compensatory action of NOS at M12. <b>Conclusions:</b> This HFD-induced neurogliovascular uncoupling pathway offers therapeutic targets to consider for improving cerebral vasoactive functions while preventing peripheral metabolic disturbances. |
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| ISSN: | 2227-9059 |