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

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 unde...

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Published in:PloS one 2021-11, Vol.16 (11), p.e0259938-e0259938
Main Authors: Redaelli, Veronica, Bosi, Alice, Luzi, Fabio, Cappella, Paolo, Zerbi, Pietro, Ludwig, Nicola, Di Lernia, Daniele, Roughan, John Vincent, Porcu, Luca, Soranna, Davide, Parati, Gianfranco, Calvillo, Laura
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose tissue (brown)
Adipose Tissue, Brown - metabolism
Animal models
Animal models in research
Animals
Bias
Biology and Life Sciences
Body Temperature
Body Weight
Bone marrow
Brain
Brain research
Chemokine CCL2 - metabolism
Chemokine CXCL12 - metabolism
Chemokines
Constraints
CXCL12 protein
Cytokines
Diagnosis
Disease Models, Animal
Evaluation
Grooming
Handling
Handling, Psychological
Homeostasis
Hospitals
Inflammation
Investigations
Laboratory animals
Male
Medicine and Health Sciences
Metabolic pathways
Metabolism
Methods
Mice
Microglia
Monocyte chemoattractant protein 1
Nervous system diseases
Neuroinflammatory Diseases - etiology
Neuroinflammatory Diseases - immunology
Neuroinflammatory Diseases - psychology
Parameter sensitivity
Physiology
Rehabilitation
Research and Analysis Methods
Restraint, Physical
Social Sciences
Software
Stress
Thermography
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Summary: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). 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0259938