Regular exposure to a Citrus-based sensory functional food ingredient alleviates the BOLD brain responses to acute pharmacological stress in a pig model of psychosocial chronic stress.

Sophie Menneson,Virginie Noirot,David Val-Laillet,Pierre Etienne,Regis Janvier,Yann Serrand,Nicolas Coquery

doi:10.1371/journal.pone.0243893

Abstract

Psychosocial chronic stress is a critical risk factor for the development of mood disorders. However, little is known about the consequences of acute stress in the context of chronic stress, and about the related brain responses. In the present study we examined the physio-behavioural effects of a supplementation with a sensory functional food ingredient (FI) containing Citrus sinensis extract (D11399, Phodé, France) in a pig psychosocial chronic stress model. Female pigs underwent a 5- to 6-week stress protocol while receiving daily the FI (FI, n = 10) or a placebo (Sham, n = 10). We performed pharmacological magnetic resonance imaging (phMRI) to study the brain responses to an acute stress (injection of Synacthen®, a synthetic ACTH-related agonist) and to the FI odour with or without previous chronic supplementation. The olfactory stimulation with the ingredient elicited higher brain responses in FI animals, demonstrating memory retrieval and habituation to the odour. Pharmacological stress with Synacthen injection resulted in an increased activity in several brain regions associated with arousal, associative learning (hippocampus) and cognition (cingulate cortex) in chronically stressed animals. This highlighted the specific impact of acute stress on the brain. These responses were alleviated in animals previously supplemented by the FI during the entire chronic stress exposure. As chronic stress establishes upon the accumulation of acute stress events, any attenuation of the brain responses to acute stress can be interpreted as a beneficial effect, suggesting that FI could be a viable treatment to help individuals coping with repeated stressful events and eventually to reduce chronic stress. This study provides additional evidence on the potential benefits of this FI, of which the long-term consequences in terms of behaviour and physiology need to be further investigated.

Highlights

Psychosocial stress is of major concern in modern life conditions
In previous studies using respectively fluoro-deoxy-glucose (FDG) positron emission tomography (PET) [32] and functional magnetic resonance imaging [21], we have shown that olfactogustatory and olfactory stimulation with a food ingredient mainly composed of Citrus sinensis extracts was notably able to modulate the reward and motivational brain circuit, that are usually impaired in chronic stress and depression resulting to anhedonia
food ingredient (FI) animals had higher brain responses in brain regions involved in associative learning and emotional processing, such as the Hippocampus (HPC), Parahippocampal Cortex (PHC) and Amygdala (AMY), as well as in the dorso-lateral Prefrontal Cortex (DL-PFC)

Summary

Introduction

Psychosocial stress is of major concern in modern life conditions. when repeated or prolonged, chronic stress is highly associated with the development of mood disorders (i.e. anxiety, depression) and other pathologies (i.e. metabolic, gastrointestinal, etc.) [1]. Mood disorders have been extensively studied in different rodent chronic stress models where the onset of depressive- and anxiety-like behaviours is described. They are notably associated with an increased hypothalamo-pituitary-adrenal (HPA) axis secreting activity, monoamines imbalance, and a decreased hippocampal neurogenesis [2,3,4,5]. These alterations have been observed in human patients [6,7,8]. There are evidences that people suffering from mood disorders might have difficulties to cope with new stressful situations [9, 10]

Results

Discussion

Conclusion