α7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Aβ peptides and promotes cerebrovascular amyloid angiopathy

Clifford, Peter; Siu, Gilbert; Kosciuk, Mary C.; Levin, Eli C.; Venkataraman, V.; D’Andrea, Michael R.; Nagele, Robert G.

doi:10.1016/j.brainres.2008.07.092

Cited by 39 publications

(27 citation statements)

References 84 publications

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“…The restricted distribution of Aβ within brain when compared to dextran (cascade blue) may reflect Aβ/Aβ receptor interactions, which promote cellular interaction, retention within brain or clearance (Deane et al, 2004; Kanekiyo and Bu, 2014; Kanekiyo et al, 2013). Multiple cell types (e.g., vascular smooth muscle cells, endothelial cells, astrocytes, microglia and neurons) express several types of Aβ receptors, such as low-density lipoprotein receptor-related protein-1 (LRP1), receptor for advanced glycation end products (RAGE) and α7 nicotinic acetylcholine receptor (Clifford et al, 2008; Deane et al, 2005; Kanekiyo and Bu, 2014; Kanekiyo et al, 2013). As Aβ flows along the perivascular space, capillaries and veins interaction with LRP1, for example, may lead to cellular uptake and transcytosis into blood (Cirrito et al, 2005a; Deane et al, 2005; Deane et al, 2004; Kanekiyo et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease

Peng

Achariyar

et al. 2016

Neurobiology of Disease

437

393

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Glymphatic transport, defined as cerebrospinal fluid (CSF) peri-arterial inflow into brain, and interstitial fluid (ISF) clearance, is reduced in the aging brain. However, it is unclear whether glymphatic transport affects the distribution of soluble Aβ in Alzheimer’s disease (AD). In wild type mice, we show that Aβ40 (fluorescently labeled Aβ40 or unlabeled Aβ40), was distributed from CSF to brain, via the peri-arterial space, and associated with neurons. In contrast, Aβ42 was mostly restricted to the peri-arterial space due mainly to its greater propensity to oligomerize when compared to Aβ40. Interestingly, pretreatment with Aβ40 in the CSF, but not Aβ42, reduced CSF transport into brain. In APP/PS1 mice, a model of AD, with and without extensive amyloid-β deposits, glymphatic transport was reduced, due to the accumulation of toxic Aβ species, such as soluble oligomers. CSF-derived Aβ40 co-localizes with existing endogenous vascular and parenchymal amyloid-β plaques, and thus, may contribute to the progression of both cerebral amyloid angiopathy and parenchymal Aβ accumulation. Importantly, glymphatic failure preceded significant amyloid-β deposits, and thus, may be an early biomarker of AD. By extension, restoring glymphatic inflow and ISF clearance are potential therapeutic targets to slow the onset and progression of AD.

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Section: Discussionmentioning

confidence: 99%

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease

Peng

Achariyar

et al. 2016

Neurobiology of Disease

437

393

View full text Add to dashboard Cite

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“…We detected α7nAChR expression in aorta VSMCs, in line with a previous study showing α7nAChR expression in brain vessels VSMCs. 37 Using a selective agonist, we examined the action of α7nAChR activation on Ang II-induced VSMC senescence. Ang II treatment increased SA-β-gal senescent staining, enhanced phosphorylation of H2A.X at Ser 139 site and Chk1 at Ser 317 site, promoted oxidative stress levels, and triggered p53-p21 and p16…”

Section: Discussionmentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Relieves Angiotensin II–Induced Senescence in Vascular Smooth Muscle Cells by Raising Nicotinamide Adenine Dinucleotide–Dependent SIRT1 Activity

Huang

et al. 2016

ATVB

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Objective-α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end-organ damage.In this study, we tested the role of α7nAChR in angiotensin II (Ang II)-induced senescence of vascular smooth muscle cells (VSMCs). Approach and Results-Expression of α7nAChR was not influenced by Ang II. Ang II induced remarkable senescent phenotypes in rodent and human VSMCs, including increased senescence-associated β-galactosidase activity, phosphorylation of H2A.X Ser139, phosphorylation of Chk1 Ser317, reduced replication, and downregulation of proliferating cell nuclear antigen. Activation of α7nAChR with a selective agonist PNU-282987 blocked Ang II-induced senescence in cultured VSMCs. Moreover, PNU-282987 treatment attenuated the Ang II infusion-induced VSMC senescence in wildtype but not in α7nAChR −/− mice. PNU-282987 reduced the Ang II-enhanced reactive oxygen species, lipid peroxidation, and the expression of NADPH oxidase 1, NADPH oxidase 4, and p22 phox in cultured VSMCs isolated from wild-type but not in α7nAChR −/− mice. Furthermore, PNU-282987 diminished Ang II-induced prosenescence signaling pathways, including p53, acetyl-p53, p21, and p16 INK4a. Finally, although α7nAChR activation by PNU-282987 did not affect the Ang II-induced downregulation of sirtuin 1 (SIRT1), it significantly increased intracellular NAD + levels, and thereby enhanced SIRT1 activity in an AMP-dependent protein kinase-independent manner. Depletion of SIRT1 by knockdown or SIRT1 inhibitor EX527 abrogated the antisenescence effect of α7nAChR against Ang II. Conclusions-Our

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“…On the other hand, some results suggest that the administration of a7 agonists/antagonists may be protective against amyloid-b toxicity (Counts et al, 2007;Mufson et al, 2008;Søderman et al, 2008). a7 nAChRs also have a role in cerebrovascular amyloid angiopathy (the deposition of amyloid-b in the cerebral vessel's wall, which is significantly more frequent in AD compared to normal aging), while the expression of a7 nAChRs by smooth muscle cells in the walls of blood vessels may facilitate the selective accumulation of amyloid-b peptides in these cells (Clifford et al, 2008). In mouse models of AD, the expression levels of the a7 nAChR protein/mRNA in the brain are also unclear (levels are elevated in the hAChE-Tg, APP SWE Tg, and APP SWE /hAChE-Tg mouse strains, but decreased in the 3xTG-AD mouse strain) (Mousavi and Nordberg, 2006;Oddo et al, 2005).…”

Section: Neuropathological Findings and Alterations Of The Cholinergimentioning

confidence: 95%

Smoking, nicotine and neuropsychiatric disorders

Döme

Lazáry

Kalapos³

et al. 2010

Neuroscience & Biobehavioral Reviews

196

140

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α7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Aβ peptides and promotes cerebrovascular amyloid angiopathy

Cited by 39 publications

References 84 publications

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease

α7 Nicotinic Acetylcholine Receptor Relieves Angiotensin II–Induced Senescence in Vascular Smooth Muscle Cells by Raising Nicotinamide Adenine Dinucleotide–Dependent SIRT1 Activity

Smoking, nicotine and neuropsychiatric disorders

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