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Vascular α1A adrenergic receptors as a potential therapeutic target for IPAD in Alzheimer's disease

Vascular α1A adrenergic receptors as a potential therapeutic target for IPAD in Alzheimer's disease
Vascular α1A adrenergic receptors as a potential therapeutic target for IPAD in Alzheimer's disease

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer's disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.

Cerebral blood vessels, Intramural periarterial drainage, α adrenergic receptor
1424-8247
1-14
Frost, Miles
c88c8e5f-9aa5-4be7-95ae-1e20dee7efd0
Keable, Abby
334f0dca-e41d-4c17-9435-df52bab191b2
Baseley, Dan
81f0c399-1a06-406e-b485-180718fde287
Sealy, Amber
84516ae4-0ea8-4f65-a55f-dfc8d98bcc17
Andreea Zbarcea, Diana
a8790592-154d-40bc-97ae-4ea1e511c44b
Gatherer, Maureen
b0aae216-21c4-4737-b042-865a65658f06
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Sharp, Matt MacGregor
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Attems, Johannes
03a5a37f-79eb-4350-b6ab-ffa1999279ab
Smith, Colin
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Chiarot, Paul R
315f3c8d-b659-48c9-a1cd-595941b4bae7
Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa
Frost, Miles
c88c8e5f-9aa5-4be7-95ae-1e20dee7efd0
Keable, Abby
334f0dca-e41d-4c17-9435-df52bab191b2
Baseley, Dan
81f0c399-1a06-406e-b485-180718fde287
Sealy, Amber
84516ae4-0ea8-4f65-a55f-dfc8d98bcc17
Andreea Zbarcea, Diana
a8790592-154d-40bc-97ae-4ea1e511c44b
Gatherer, Maureen
b0aae216-21c4-4737-b042-865a65658f06
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Sharp, Matt MacGregor
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Attems, Johannes
03a5a37f-79eb-4350-b6ab-ffa1999279ab
Smith, Colin
d991039c-1c8b-4aff-a306-b45c67c486e9
Chiarot, Paul R
315f3c8d-b659-48c9-a1cd-595941b4bae7
Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa

Frost, Miles, Keable, Abby, Baseley, Dan, Sealy, Amber, Andreea Zbarcea, Diana, Gatherer, Maureen, Yuen, Ho Ming, Sharp, Matt MacGregor, Weller, Roy O, Attems, Johannes, Smith, Colin, Chiarot, Paul R and Carare, Roxana O (2020) Vascular α1A adrenergic receptors as a potential therapeutic target for IPAD in Alzheimer's disease. Pharmaceuticals, 13 (9), 1-14, [261]. (doi:10.3390/ph13090261).

Record type: Article

Abstract

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer's disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.

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More information

Accepted/In Press date: 19 September 2020
Published date: 22 September 2020
Keywords: Cerebral blood vessels, Intramural periarterial drainage, α adrenergic receptor

Identifiers

Local EPrints ID: 444954
URI: http://eprints.soton.ac.uk/id/eprint/444954
ISSN: 1424-8247
PURE UUID: c62f48e1-46f3-4d54-ac7b-7492e5e9ac87
ORCID for Matt MacGregor Sharp: ORCID iD orcid.org/0000-0002-6623-5078
ORCID for Roxana O Carare: ORCID iD orcid.org/0000-0001-6458-3776

Catalogue record

Date deposited: 12 Nov 2020 17:33
Last modified: 26 Nov 2021 02:55

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Contributors

Author: Miles Frost
Author: Abby Keable
Author: Dan Baseley
Author: Amber Sealy
Author: Diana Andreea Zbarcea
Author: Maureen Gatherer
Author: Ho Ming Yuen
Author: Matt MacGregor Sharp ORCID iD
Author: Roy O Weller
Author: Johannes Attems
Author: Colin Smith
Author: Paul R Chiarot
Author: Roxana O Carare ORCID iD

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