eprintid: 10163033
rev_number: 10
eprint_status: archive
userid: 699
dir: disk0/10/16/30/33
datestamp: 2023-01-12 09:39:56
lastmod: 2024-01-04 16:24:09
status_changed: 2023-01-12 09:39:56
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Martins Sá, Renato W
creators_name: Theparambil, Shefeeq M
creators_name: Dos Santos, Karoline Martins
creators_name: Christie, Isabel N
creators_name: Marina, Nephtali
creators_name: Cardoso, Barbara V
creators_name: Hosford, Patrick S
creators_name: Antunes, Vagner R
title: Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
keywords: Adenosine, Astrocytes, ATP, Hypothalamus, Salt-loading
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Previously, we have shown that purinergic signalling is involved in the control of hyperosmotic-induced sympathoexcitation at the level of the PVN, via activation of P2X receptors. However, the source(s) of ATP that drives osmotically-induced increases in sympathetic outflow remained undetermined. Here, we tested the two competing hypotheses that either (1) higher extracellular ATP in PVN during salt loading (SL) is a result of a failure of ectonucleotidases to metabolize ATP; and/or (2) SL can stimulate PVN astrocytes to release ATP. Rats were salt loaded with a 2 % NaCl solution replacing drinking water up to 4 days, an experimental model known to cause a gradual increase in blood pressure and plasma osmolarity. Immunohistochemical assessment of glial-fibrillary acidic protein (GFAP) revealed increased glial cell reactivity in the PVN of rats after 4 days of high salt exposure. ATP and adenosine release measurements via biosensors in hypothalamic slices showed that baseline ATP release was increased 17-fold in the PVN while adenosine remained unchanged. Disruption of Ca2+-dependent vesicular release mechanisms in PVN astrocytes by virally-driven expression of a dominant-negative SNARE protein decreased the release of ATP. The activity of ectonucleotidases quantified in vitro by production of adenosine from ATP was increased in SL group. Our results showed that SL stimulates the release of ATP in the PVN, at least in part, from glial cells by a vesicle-mediated route and likely contributes to the neural control of circulation during osmotic challenges.
date: 2023-03
date_type: published
publisher: Elsevier
official_url: https://doi.org/10.1016/j.mcn.2022.103806
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1999355
doi: 10.1016/j.mcn.2022.103806
medium: Print-Electronic
pii: S1044-7431(22)00112-9
lyricists_name: Marina-Gonzalez, Nephtali
lyricists_id: NGMAR80
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Molecular and Cellular Neuroscience
volume: 124
article_number: 103806
event_location: United States
issn: 1044-7431
citation:        Martins Sá, Renato W;    Theparambil, Shefeeq M;    Dos Santos, Karoline Martins;    Christie, Isabel N;    Marina, Nephtali;    Cardoso, Barbara V;    Hosford, Patrick S;           Martins Sá, Renato W;  Theparambil, Shefeeq M;  Dos Santos, Karoline Martins;  Christie, Isabel N;  Marina, Nephtali;  Cardoso, Barbara V;  Hosford, Patrick S;  Antunes, Vagner R;   - view fewer <#>    (2023)    Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats.                   Molecular and Cellular Neuroscience , 124     , Article 103806.  10.1016/j.mcn.2022.103806 <https://doi.org/10.1016/j.mcn.2022.103806>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10163033/1/1-s2.0-S1044743122001129-main.pdf