Diet-induced obesity has neuroprotective effects in murine gastric enteric nervous system: involvement of leptin and glial cell line-derived neurotrophic factor
Diet-induced obesity has neuroprotective effects in murine gastric enteric nervous system: involvement of leptin and glial cell line-derived neurotrophic factor
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DOI：
10.1113/jphysiol.2011.219717
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发表时间：
2012-02-01
影响因子：
5.5
通讯作者：
Moriez, Raphael
中科院分区：
文献类型：
--
作者：
Baudry, Charlotte;Reichardt, Francois;Moriez, Raphael
营养因素可诱导肠神经系统（ENS）发生深刻的神经可塑性变化，导致胃肠（GI）运动的变化。然而，长期影响营养失衡导致肥胖，如西方饮食（WD）后ENS表型和控制胃肠道动力仍然未知。因此，我们研究了WD诱导的肥胖（DIO）对ENS表型和功能以及功能可塑性相关因素的影响。用正常饲料（ND）或WD喂养小鼠12周。在体内和离体评估GI运动性。肌间神经元和神经胶质细胞进行了分析与免疫组化方法，使用抗体对胡，神经元型一氧化氮合酶（nNOS），Sox-10和钙成像技术。用免疫组织化学、生物化学和PCR方法研究了瘦素和胶质细胞源性神经营养因子（GDNF）在小鼠和原代培养的ENS中的表达。DIO预防了ND小鼠胃窦氮能神经元的年龄相关性减少。神经刺激诱发了更强的神经元Ca 2+的反应，在WD相比，ND小鼠。DIO诱导NO依赖性胃排空和胃窦神经肌肉传递增加，而小肠转运无任何变化。在WD而不是ND期间，胃窦中的瘦素和GDNF呈时间依赖性增加。最后，我们发现，瘦素增加GDNF的生产在ENS和诱导的神经保护作用，部分介导的GDNF。这些结果表明，DIO诱导胃窦中的神经可塑性变化，导致NO依赖性胃排空加速。此外，DIO诱导的ENS中的神经可塑性可能涉及瘦素和GDNF。
Nutritional factors can induce profound neuroplastic changes in the enteric nervous system(ENS), responsible for changes in gastrointestinal (GI) motility. However, long-term effects of a nutritional imbalance leading to obesity, such as Western diet (WD), upon ENS phenotype and control of GI motility remain unknown. Therefore, we investigated the effects of WD-induced obesity (DIO) on ENS phenotype and function as well as factors involved in functional plasticity. Mice were fed with normal diet (ND) or WD for 12 weeks. GI motility was assessed in vivo and ex vivo. Myenteric neurons and glia were analysed with immunohistochemical methods using antibodies against Hu, neuronal nitric oxide synthase (nNOS), Sox-10 and with calcium imaging techniques. Leptin and glial cell line-derived neurotrophic factor (GDNF) were studied using immunohistochemical, biochemical or PCR methods in mice and primary culture of ENS. DIO prevented the age-associated decrease in antral nitrergic neurons observed in ND mice. Nerve stimulation evoked a stronger neuronal Ca2+ response in WD compared to ND mice. DIO induced an NO-dependent increase in gastric emptying and neuromuscular transmission in the antrum without any change in small intestinal transit. During WD but not ND, a time-dependent increase in leptin and GDNF occurred in the antrum. Finally, we showed that leptin increased GDNF production in the ENS and induced neuroprotective effects mediated in part by GDNF. These results demonstrate that DIO induces neuroplastic changes in the antrum leading to an NO-dependent acceleration of gastric emptying. In addition, DIO induced neuroplasticity in the ENS is likely to involve leptin and GDNF.