| First Author | Madison CA | Year | 2023 |
| Journal | Behav Brain Res | Volume | 440 |
| Pages | 114256 | PubMed ID | 36528169 |
| Mgi Jnum | J:351412 | Mgi Id | MGI:7413702 |
| Doi | 10.1016/j.bbr.2022.114256 | Citation | Madison CA, et al. (2022) Intestinal epithelium aryl hydrocarbon receptor is involved in stress sensitivity and maintaining depressive symptoms. Behav Brain Res 440:114256 |
| abstractText | The aryl hydrocarbon receptor (AhR) is a key regulator in the microbiome-gut-brain axis, and AhR-active microbial metabolites modulate multiple neuronal responses. We recently demonstrated that 3,3'-diindolylmethane (DIM) and 1,4-dihydroxy-2-naphthoic acid (DHNA), two selective AhR modulators (SAhRMs), act as antidepressants in female mice. Thus, to examine the role of intestinal AhR in depression, anxiety, and spatial learning, this study employed transgenic mice in which the AhR was knockout only in the intestinal epithelium (AhRDeltaIEC). Additionally, this study examined whether the antidepressant effects of dietary DIM and DHNA is mediated by intestinal AhR. AhRDeltaIEC and WT female mice were fed daily with vehicle, 20 mg/kg DIM or DHNA for three weeks prior to four weeks of unpredictable chronic mild stress (UCMS). Mice were examined for weight gain, anhedonia-like behavior (sucrose preference test), anxiety levels (open field, light/dark, elevated plus maze, novelty-induced hypophagia, and marble burying tests), and spatial learning (Morris water maze). UCMS reduced weight gain in AhRDeltaIECs, but not WTs. Moreover, UCMS initially reduced sucrose preference in both AhRDeltaIECs and WTs, but over 4 weeks of UCMS, AhRDeltaIECs develop resilience to UCMS-induced anhedonia. Additionally, AhRDeltaIECs exhibit slightly reduced anxiety in certain tests and faster spatial learning. DIM and DHNA acted as antidepressants in both AhRDeltaIECs and WTs. Thus, this study suggests that intestinal AhR plays differential roles, mitigating stress effects on weight gain, and increasing stress effects on mood. However, the site of antidepressant action of SAhRMs, such as DIM and DHNA, is not dependent on the expression of intestinal AhR. |
