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

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.

Exposure to a sensory functional ingredient in the pig model modulates the blood-oxygen-level dependent brain responses to food odor and acute stress during pharmacological MRI in the frontostriatal and limbic circuits

“…Functional food ingredients derived from natural extracts are of growing interest in human and animal nutrition to optimize food intake and improve well-being through adaptation to potential stressors for example (1). Usually composed of aromatic substances (essential oils, aromatic herbs, spices, etc.…”

“…In previous preclinical studies in a pig model of chronic psychosocial stress characterized by social isolation, environment impoverishment and unpredictability (10), we have shown that functional food ingredients (FI) based on spice extracts (Curcuma longa L., Piper nigrum L., Capsicum annuum L., and Zingiber officinale L.) or Citrus sinensis could induce food preference and have possible anxiolytic properties, while modulating brain activity and plasticity in regions involved in pleasure, emotion regulation and cognition (1,11). Indeed, animals that had supplemented feed with a functional ingredient had a lower number of escape attempts within the openfield test arena and a lower latency to eat during the novelty-suppressed feeding test compared to the control group (11).…”

Impact of a Dietary Citrus Extract on the Behavior and Production of Lactating Dairy Cows Following Regrouping: A Preliminary Study

“…In support of that, Val-Laillet et al ( 17 ) demonstrated that feeding pigs a C. sinensis based CE feed additive had positive impacts on brain activation in the insular cortex, the amygdala, and the striatum (putamen and caudate), suggesting that the CE stimulated reward perception and anticipation in pigs. Finally, an imaging study in pigs treated with a C. sinensis based CE feed demonstrated that olfactory stimulation induced by this ingredient increases the activity of several brain regions associated with the regulation of cognitive and emotional processes ( 14 ).…”

“…Exposure to citrus extract (CE) essential oil, derived from Citrus sinensis ("sweet orange"), has been demonstrated to reduce anxiety in male Wistar rats (12) and reduce mean blood pressure, respiratory rate, and pulse rate in children during a stressful situation (13). Similarly, Menneson et al (14) demonstrated that pigs that exposed to CE had a lesser stress response when injected with a substance to induce stress than pigs not exposed to CE. Perhaps most compellingly, Lehrner et al (15) observed that, in a study of men and women, diffusing C. sinensis essential oil into a dental office waiting room reduced self-reporting of anxiety and increased reporting of factors associated with positive mood (n = 50 subjects) compared with a control (no scent; n = 51 subjects).…”

Acute Effects of Different Electroacupuncture Point Combinations to Modulate the Gut-Brain Axis in the Minipig Model

“…In our study, we chose to use the minipig model because this species presents many similarities with the human in terms of organ size and proportions, notably gastrointestinal tract anatomy, morphology, and physiology, besides having a quite large gyrencephalic brain better suited for brain functional imaging [10,11]. Our INRAE research group gained renowned expertise on the minipig model for nutrition and neuroscience research and have implemented various in vivo brain imaging strategies to explore in pigs the brain activity and metabolism in response to olfactogustatory and other kinds of relevant stimulations [12][13][14] but also in the context of diet-induced obesity [11,15]. In a recent review paper, we presented the obesity animal models for acupuncture and related therapy research studies [1].…”