The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

被引:9
作者
Lobo, Beatriz [1 ,5 ,6 ,7 ]
Tramullas, Monica [1 ,8 ]
Finger, Beate-C [1 ]
Lomasney, Kevin W. [1 ,3 ]
Beltran, Caroll [1 ,9 ]
Clarke, Gerard [1 ]
Santos, Javier [5 ,6 ,7 ,10 ]
Hyland, Niall P. [1 ,2 ]
Dinan, Timothy G. [1 ,4 ]
Cryan, John F. [1 ,3 ]
机构
[1] Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland
[2] Univ Coll Cork, Dept Physiol, Cork, Ireland
[3] Univ Coll Cork, Dept Anat & Neurosci, Cork, Ireland
[4] Univ Coll Cork, Dept Psychiat & Neurobehav Sci, Cork, Ireland
[5] Vall Hebron Hosp Univ, Vall Hebron Inst Recerca VHIR, Digest Syst Res Unit, Lab Neuroimmuno Gastroenterol, Barcelona, Spain
[6] Vall Hebron Hosp Univ, Dept Gastroenterol, Barcelona, Spain
[7] Univ Autonoma Barcelona, Fac Med, Barcelona, Spain
[8] Univ Cantabria, Fac Med, Dept Fisiol & Farmacol, Santander, Spain
[9] Univ Chile, Hosp Clin, Fac Med, Lab Immunogastroenterol,Gastroenterol Unit, Santiago, Chile
[10] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 08035, Spain
基金
爱尔兰科学基金会;
关键词
Enteric nervous system; Gastrointestinal motility; Nerve tissue proteins; Neuronal plasticity; Stress; psychological; NEUROTROPHIC FACTOR CONTRIBUTES; IRRITABLE-BOWEL-SYNDROME; ENTERIC GLIAL-CELLS; BRAIN AXIS; VISCERAL PAIN; SOCIAL STRESS; RAT MODEL; MICROBIOTA; CONSTIPATION; DISORDERS;
D O I
10.5056/jnm22009
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims Chronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear. This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function.Methods Adult male C57BL/6J mice were exposed to 19 day of unpredictable stress protocol schedule of social defeat and overcrowding. We investigated the effects on plasma corticosterone, food intake, and body weight. In vivo gastrointestinal motility was assessed by fecal pellet output and by whole-gastrointestinal transit (using the carmine red method). Tissue monoamine level, neural and glial markers, neurotrophic factors, monoamine signaling, and Toll-like receptor expression in the proximal and distal colon, and terminal ileum were also assessed.Results Following chronic unpredictable psychological stress, stressed mice showed increased food intake and body weight gain (P < 0.001), and reduced corticosterone levels (P < 0.05) compared to control mice. Stressed mice had reduced stool output without differences in water content, and showed a delayed gastrointestinal transit compared to control mice (P < 0.05). Stressed mice exhibited decreased mRNA expression of tyrosine hydroxylase (Th), brain-derived neurotrophic factor (Bdnf) and glial cell-derived neurotrophic factor (Gdnf), as well as Toll-like receptor 2 (Tlr2) compared to control (P < 0.05), only proximal colon. These molecular changes in proximal colon were associated with higher levels of monoamines in tissue. Conclusion Unpredictable psychological chronic stress induces region-specific impairment in monoamine levels and neuroplasticity markers that may relate to delayed intestinal transit. (J Neurogastroenterol Motil 2023;29:72-84)
引用
收藏
页码:72 / 84
页数:13
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