Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study

<h4>Background</h4> Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those invol...

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Autores principales:	Veronica Redaelli, Alice Bosi, Fabio Luzi, Paolo Cappella, Pietro Zerbi, Nicola Ludwig, Daniele Di Lernia, John Vincent Roughan, Luca Porcu, Davide Soranna, Gianfranco Parati, Laura Calvillo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08b1230596334e749b03ec4d5ed54e15
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spelling	oai:doaj.org-article:08b1230596334e749b03ec4d5ed54e152021-11-25T05:54:26ZNeuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study1932-6203https://doaj.org/article/08b1230596334e749b03ec4d5ed54e152021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592432/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4> Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those involving restraint may generate undesired effects which may act as a source of bias. However, the extent to which potentially confounding effects derive from such routine procedures is currently unknown. Our study was therefore aimed at exploring possible undesirable effects of acute restraint stress, whereby animals were exposed to a brightly lit enclosed chamber (R&L) similar to those that are commonly used for substance injection. We hypothesised that this would induce a range of unwanted physiological alterations [such as neuroinflammatory response and changes in body weight and in brown adipose tissue (BAT)] and behavioural modification, and that these might be mitigated via the use of non-aversive handling methods: Tunnel Handling (NAH-T) and Mechanoceptive Handling (NAH-M)) as compared to standard Tail Handling (TH). <h4>Methods</h4> Two indicators of physiological alterations and three potentially stress sensitive behavioural parameters were assessed. Physiological alterations were recorded via body weight changes and assessing the temperature of Brown Adipose Tissue (BAT) using infra-red thermography (IRT), and at the end of the experiment we determined the concentration of cytokines CXCL12 and CCL2 in bone marrow (BM) and activated microglia in the brain. Nest complexity scoring, automated home-cage behaviour analysis (HCS) and Elevated Plus Maze testing (EPM) were used to detect any behavioural alterations. Recordings were made before and after a 15-minute period of R&L in groups of mice handled via TH, NAH-T or NAH-M. <h4>Results</h4> BAT temperature significantly decreased in all handling groups following R&L regardless of handling method. There was a difference, at the limit of significance (p = 0.06), in CXCL12 BM content among groups. CXCL12 content in BM of NAH-T animals was similar to that found in Sentinels, the less stressed group of animals. After R&L, mice undergoing NAH-T and NAH-M showed improved body-weight maintenance compared to those exposed to TH. Mice handled via NAH-M spent a significantly longer time on the open arms of the EPM. The HCS results showed that in all mice, regardless of handling method, R&L resulted in a significant reduction in walking and rearing, but not in total distance travelled. All mice also groomed more. No difference among the groups was found in Nest Score, in CCL2 BM content or in brain activated microglia. <h4>Conclusions</h4> Stress induced by a common restraint procedure caused metabolic and behavioural changes that might increase the risk of unexpected bias. In particular, the significant decrease in BAT temperature could affect the important metabolic pathways controlled by this tissue. R&L lowered the normal frequency of walking and rearing, increased grooming and probably carried a risk of low-grade neuro-inflammation. Some of the observed alterations can be mitigated by Non-aversive handlings.Veronica RedaelliAlice BosiFabio LuziPaolo CappellaPietro ZerbiNicola LudwigDaniele Di LerniaJohn Vincent RoughanLuca PorcuDavide SorannaGianfranco ParatiLaura CalvilloPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Veronica Redaelli Alice Bosi Fabio Luzi Paolo Cappella Pietro Zerbi Nicola Ludwig Daniele Di Lernia John Vincent Roughan Luca Porcu Davide Soranna Gianfranco Parati Laura Calvillo Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
description	<h4>Background</h4> Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those involving restraint may generate undesired effects which may act as a source of bias. However, the extent to which potentially confounding effects derive from such routine procedures is currently unknown. Our study was therefore aimed at exploring possible undesirable effects of acute restraint stress, whereby animals were exposed to a brightly lit enclosed chamber (R&L) similar to those that are commonly used for substance injection. We hypothesised that this would induce a range of unwanted physiological alterations [such as neuroinflammatory response and changes in body weight and in brown adipose tissue (BAT)] and behavioural modification, and that these might be mitigated via the use of non-aversive handling methods: Tunnel Handling (NAH-T) and Mechanoceptive Handling (NAH-M)) as compared to standard Tail Handling (TH). <h4>Methods</h4> Two indicators of physiological alterations and three potentially stress sensitive behavioural parameters were assessed. Physiological alterations were recorded via body weight changes and assessing the temperature of Brown Adipose Tissue (BAT) using infra-red thermography (IRT), and at the end of the experiment we determined the concentration of cytokines CXCL12 and CCL2 in bone marrow (BM) and activated microglia in the brain. Nest complexity scoring, automated home-cage behaviour analysis (HCS) and Elevated Plus Maze testing (EPM) were used to detect any behavioural alterations. Recordings were made before and after a 15-minute period of R&L in groups of mice handled via TH, NAH-T or NAH-M. <h4>Results</h4> BAT temperature significantly decreased in all handling groups following R&L regardless of handling method. There was a difference, at the limit of significance (p = 0.06), in CXCL12 BM content among groups. CXCL12 content in BM of NAH-T animals was similar to that found in Sentinels, the less stressed group of animals. After R&L, mice undergoing NAH-T and NAH-M showed improved body-weight maintenance compared to those exposed to TH. Mice handled via NAH-M spent a significantly longer time on the open arms of the EPM. The HCS results showed that in all mice, regardless of handling method, R&L resulted in a significant reduction in walking and rearing, but not in total distance travelled. All mice also groomed more. No difference among the groups was found in Nest Score, in CCL2 BM content or in brain activated microglia. <h4>Conclusions</h4> Stress induced by a common restraint procedure caused metabolic and behavioural changes that might increase the risk of unexpected bias. In particular, the significant decrease in BAT temperature could affect the important metabolic pathways controlled by this tissue. R&L lowered the normal frequency of walking and rearing, increased grooming and probably carried a risk of low-grade neuro-inflammation. Some of the observed alterations can be mitigated by Non-aversive handlings.
format	article
author	Veronica Redaelli Alice Bosi Fabio Luzi Paolo Cappella Pietro Zerbi Nicola Ludwig Daniele Di Lernia John Vincent Roughan Luca Porcu Davide Soranna Gianfranco Parati Laura Calvillo
author_facet	Veronica Redaelli Alice Bosi Fabio Luzi Paolo Cappella Pietro Zerbi Nicola Ludwig Daniele Di Lernia John Vincent Roughan Luca Porcu Davide Soranna Gianfranco Parati Laura Calvillo
author_sort	Veronica Redaelli
title	Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
title_short	Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
title_full	Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
title_fullStr	Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
title_full_unstemmed	Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study
title_sort	neuroinflammation, body temperature and behavioural changes in cd1 male mice undergoing acute restraint stress: an exploratory study
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/08b1230596334e749b03ec4d5ed54e15
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Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study

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