Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists.
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, o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00422/full |
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| author | Jorge Navarro-Dorado Nuria Villalba Dolores Prieto Begoña Brera Ana María Martín-Moreno Teresa Tejerina Maria L. De Ceballos |
| author_facet | Jorge Navarro-Dorado Nuria Villalba Dolores Prieto Begoña Brera Ana María Martín-Moreno Teresa Tejerina Maria L. De Ceballos |
| author_sort | Jorge Navarro-Dorado |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T06:44:44Z |
| format | Article |
| id | doaj.art-68b4b1df0cc143a69f0385c5148db9ec |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T06:44:44Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-68b4b1df0cc143a69f0385c5148db9ec2022-12-22T02:57:37ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-09-011010.3389/fnins.2016.00422208619Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists.Jorge Navarro-Dorado0Nuria Villalba1Dolores Prieto2Begoña Brera3Ana María Martín-Moreno4Teresa Tejerina5Maria L. De Ceballos6School of Medicine, UCMFaculty of Pharmacy, UCMFaculty of Pharmacy, UCMCajal Institute, CSICCajal Institute, CSICSchool of Medicine, UCMCajal Institute, CSICThere 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.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00422/fullbeta-amyloidVascular DysfunctionAlzheimer's disease (AD)cannabioid receptorsTg APP |
| spellingShingle | Jorge Navarro-Dorado Nuria Villalba Dolores Prieto Begoña Brera Ana María Martín-Moreno Teresa Tejerina Maria L. De Ceballos Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. Frontiers in Neuroscience beta-amyloid Vascular Dysfunction Alzheimer's disease (AD) cannabioid receptors Tg APP |
| title | Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. |
| title_full | Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. |
| title_fullStr | Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. |
| title_full_unstemmed | Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. |
| title_short | Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists. |
| title_sort | vascular dysfunction in a transgenic model of alzheimer s disease effects of cb1r and cb2r cannabinoid agonists |
| topic | beta-amyloid Vascular Dysfunction Alzheimer's disease (AD) cannabioid receptors Tg APP |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00422/full |
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