Subchronic and mild social defeat stress downregulates peripheral expression of sweet and umami taste receptors in male mice
Introduction
Depression is one of the most common disorders, affecting >264 million people worldwide [1]. Chronic social and psychological stress is a major cause of depressive disorders in humans; however, our understanding of the pathophysiological mechanisms of depression is limited. One of the characteristic changes induced by mental stress disorders is taste dysfunction, and it has been reported that anxiety, perceived stress, and depression are associated with taste disorder [2,3]. However, the mechanisms by which mental stress affects taste-sensing systems are not well understood. Thus, this study aimed to investigate whether psychosocial stress affects peripheral taste-sensing systems, focusing on the expression of taste receptors in the gustatory papillae.
Chronic social defeat stress (CSDS) is one of the most commonly used animal models of depression [4,5]. The standard CSDS method comprises short-term physical contact by the resident-intruder paradigm (5–10 min/day) followed by long-term psychological stress conditions through visual and olfactory cues of resident mice for 10 successive days [6]. CSDS not only induces depressive-like behavior, such as social avoidance behaviors, but also shows anhedonia-like behavior, including a reduction in sucrose preference [4]. However, whether CSDS induces peripheral taste disorders has not been investigated. We have previously established a subchronic and mild social defeat stress (sCSDS) model in mice to ensure greater validity as a model of depression by minimizing physical contact and injury [7,8]. Our sCSDS paradigm consists of approximately half-scale physical stress condition (2.75 min/day on average) compared with a standard CSDS method [6], which enables us to focus on the effects of psychosocial stress.
Taste plays an important role in the pleasure of eating food and quality of life. Taste quality is classified into five basic tastes: sweet, umami, bitter, sour, and salty. Taste buds are the sensory organs for taste and are mainly located in the gustatory papillae of the tongue. Sweet and umami tastes are mediated by the T1R family and are expressed in taste sensory cells [9]. A heterodimer of taste receptor type 1 members 2 and 3 (T1R2/T1R3) mediates sweet taste, and a heterodimer of taste receptor type 1 member 1 and 3 (T1R1/T1R3) mediates umami taste [9,10]. A previous study reported that physical immobilization stress induced by chronic restraint for 8 h every 14 successive days reduced gustatory neural responses and oral expression of T1R3 in rats [11]. Thus, in the present study, we investigated the effects of sCSDS not only on reward-seeking behaviors, using the sucrose preference test (SPT) and female urine sniffing test (FUST), but also on peripheral expression levels of taste receptors, taste-signaling molecules, and taste cell markers in the gustatory papillae of mice.
Section snippets
Animals
This study was carried out according to the Law Concerning the Human Care and Control of Animals (Law No. 105; October 1, 1973), the Japanese Government Notification on the Feeding and Safekeeping of Animals (Notification No. 6; March 27, 1980), and the ARRIVE guidelines and approved by the Committee for Laboratory Animal Care and Use at Ibaraki University with the guidelines of the Experimental Animal Committee (approval nos. 20230 and 21180).
Male C57BL/6J (B6) mice (7 weeks old) and Slc:ICR
Body weight, food intake, and water intake
A two-way repeated-measures ANOVA revealed a significant effect of sCSDS on daily body weight, food intake, and water intake (Fig. 1B–D), as shown previously [7,8]. The two-way ANOVA results are summarized in Table 1. In addition, total body weight gain, total food intake, and total water intake from day 1 to day 10 were all significantly upregulated in the sCSDS mice by unpaired t-test (data not shown).
Social interaction test
The SI score was significantly decreased in the sCSDS mice (Fig. 1E), suggesting that the
Discussion
The present study investigated whether psychosocial stress affects peripheral taste-sensing systems, especially the expression of taste receptors in the gustatory papillae, and we observed that sCSDS mice showed increased body weight, food intake, and water intake and reduced social interaction behavior compared with the control mice. These results were consistent with those of our previous reports [7,8], suggesting that the mice used in the present study successfully reflected the effects of
Funding
This study was supported by grants from Atsushi Toyoda from JSPS KAKENHI [grant number 18K06011].
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing.
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