Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats
Abstract Background Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BioPsychoSocial Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13030-022-00258-x |
| _version_ | 1797864373675360256 |
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| author | Ryoko Hasegawa Kumi Saito-Nakaya Li Gu Motoyori Kanazawa Shin Fukudo |
| author_facet | Ryoko Hasegawa Kumi Saito-Nakaya Li Gu Motoyori Kanazawa Shin Fukudo |
| author_sort | Ryoko Hasegawa |
| collection | DOAJ |
| description | Abstract Background Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD). Methods Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS. Results In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline. Conclusions These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic–pituitary–adrenal axis function depending on sex. |
| first_indexed | 2024-04-09T22:50:45Z |
| format | Article |
| id | doaj.art-ba0f3fd170c24815aca843f939ffec98 |
| institution | Directory Open Access Journal |
| issn | 1751-0759 |
| language | English |
| last_indexed | 2024-04-09T22:50:45Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BioPsychoSocial Medicine |
| spelling | doaj.art-ba0f3fd170c24815aca843f939ffec982023-03-22T11:39:34ZengBMCBioPsychoSocial Medicine1751-07592023-02-0117111210.1186/s13030-022-00258-xMaternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in ratsRyoko Hasegawa0Kumi Saito-Nakaya1Li Gu2Motoyori Kanazawa3Shin Fukudo4Department of Behavioral Medicine, Tohoku University Graduate School of MedicineDepartment of Behavioral Medicine, Tohoku University Graduate School of MedicineDepartment of Behavioral Medicine, Tohoku University Graduate School of MedicineDepartment of Behavioral Medicine, Tohoku University Graduate School of MedicineDepartment of Behavioral Medicine, Tohoku University Graduate School of MedicineAbstract Background Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD). Methods Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS. Results In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline. Conclusions These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic–pituitary–adrenal axis function depending on sex.https://doi.org/10.1186/s13030-022-00258-xAttention-deficit/hyperactivity disorderCorticotropin-releasing hormoneEarly-life stressIrritable bowel syndromeMaternal separationVisceral hypersensitivity |
| spellingShingle | Ryoko Hasegawa Kumi Saito-Nakaya Li Gu Motoyori Kanazawa Shin Fukudo Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats BioPsychoSocial Medicine Attention-deficit/hyperactivity disorder Corticotropin-releasing hormone Early-life stress Irritable bowel syndrome Maternal separation Visceral hypersensitivity |
| title | Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| title_full | Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| title_fullStr | Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| title_full_unstemmed | Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| title_short | Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| title_sort | maternal separation and tnbs induced gut inflammation synergistically alter the sexually differentiated stress response in rats |
| topic | Attention-deficit/hyperactivity disorder Corticotropin-releasing hormone Early-life stress Irritable bowel syndrome Maternal separation Visceral hypersensitivity |
| url | https://doi.org/10.1186/s13030-022-00258-x |
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