Jorge Navarro-Dorado, Nuria Villalba, Dolores Prieto, Begoña Brera, Ana M. Martín-Moreno, Teresa Tejerina, María L. de Ceballos
Abstract
There is evidence of altered vascular function, including cerebrovascular, in Alzheimer's disease (AD) and transgenic models of the disease. Indeed vasoconstrictor responses are increased, while vasodilation is reduced in both conditions. β-Amyloid (Aβ) appears to be responsible, at least in part, of alterations in vascular function. Cannabinoids, neuroprotective and anti-inflammatory agents, induce vasodilation both in vivo and in vitro. We have demonstrated a beneficial effect of cannabinoids in models of AD by preventing glial activation. In this work we have studied the effects of these compounds on vessel density in amyloid precursor protein (APP) transgenic mice, line 2576, and on altered vascular responses in aortae isolated ring. First we showed increased collagen IV positive vessels in AD brain compared to control subjects, with a similar increase in TgAPP mice, which was normalized by prolonged oral treatment with the CB1/CB2 mixed agonist WIN 55,212-2 (WIN) and the CB2 selective agonist JWH-133 (JWH). In Tg APP mice the vasoconstriction induced by phenylephrine and the thromboxane agonist U46619 was significantly increased, and no change in the vasodilation to acetylcholine (ACh) was observed. Tg APP displayed decreased vasodilation to both cannabinoid agonists, which were able to prevent decreased ACh relaxation in the presence of Aβ. In summary, we have confirmed and extended the existence of altered vascular responses in Tg APP mice. Moreover, our results suggest that treatment with cannabinoids may ameliorate the vascular responses in AD-type pathology.
Pharmacology, Toxicology and Pharmaceutical Science
4
9%
Nursing and Health Professions
3
7%
Medicine and Dentistry
3
7%
Biochemistry, Genetics and Molecular Biology
2
4%
Other
6
13%
Unknown
21
47%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 October 2016.
All research outputs
#2,639,369
of 25,374,647 outputs
Outputs from Frontiers in Neuroscience
#1,650
of 11,542 outputs
Outputs of similar age
#41,656
of 315,128 outputs
Outputs of similar age from Frontiers in Neuroscience
#19
of 132 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,542 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.9. This one has done well, scoring higher than 85% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,128 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 132 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.
