Vascular oxidative stress causes neutrophil arrest in brain capillaries, leading to decreased cerebral blood flow and contributing to memory impairment in a mouse model of Alzheimer’s disease
INTRODUCTION: In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD.
METHODS: We inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used in vivo two-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels.
RESULTS: We found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways.
DISCUSSION: Oxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2023) vom: 15. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ruiz-Uribe, Nancy E [VerfasserIn] |
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| Anmerkungen: |
Date Revised 07.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2023.02.15.528710 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353309990 |
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| 041 | |a eng | ||
| 100 | 1 | |a Ruiz-Uribe, Nancy E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Vascular oxidative stress causes neutrophil arrest in brain capillaries, leading to decreased cerebral blood flow and contributing to memory impairment in a mouse model of Alzheimer’s disease |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 07.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a INTRODUCTION: In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD | ||
| 520 | |a METHODS: We inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used in vivo two-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels | ||
| 520 | |a RESULTS: We found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways | ||
| 520 | |a DISCUSSION: Oxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Bracko, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Swallow, Madisen |e verfasserin |4 aut | |
| 700 | 1 | |a Omurzakov, Argen |e verfasserin |4 aut | |
| 700 | 1 | |a Dash, Sabyasachi |e verfasserin |4 aut | |
| 700 | 1 | |a Uchida, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, David |e verfasserin |4 aut | |
| 700 | 1 | |a Haft-Javaherian, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Falkenhain, Kaja |e verfasserin |4 aut | |
| 700 | 1 | |a Lamont, Michael E |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Njiru, Brendah N |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Hsin-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Adrian Y |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Jenny Z |e verfasserin |4 aut | |
| 700 | 1 | |a Iadecola, Costantino |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Laibaik |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Nishimura, Nozomi |e verfasserin |4 aut | |
| 700 | 1 | |a Schaffer, Chris B |e verfasserin |4 aut | |
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