Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus neurons regulating gastric functions.
Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus neurons regulating gastric functions.
复制标题
围产期高脂肪饮食会增加对调节胃功能的迷走神经元背运动核的抑制。
DOI：
10.1111/nmo.13150
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Browning,KN
中科院分区：
文献类型：
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作者：
McMenamin,CA;Travagli,RA;Browning,KN
先前的研究表明，暴露于围产期高脂饮食（PNHFD）后，迷走神经背运动核（DMV）神经元的抑制增加；然而，潜在的神经机制仍然未知。本研究评估了PNHFD对DMV神经元的抑制性突触输入和胃张力和胃运动的迷走神经依赖性控制的影响。方法全细胞膜片钳记录Sprague - Dawley大鼠从胚胎第13天起饲喂对照饮食或HFD（分别为14%或60%卡路里来自脂肪）的薄脑干切片的DMV神经元；在体内麻醉大鼠，记录胃张力和胃运动。非选择性gaba拮抗剂BIC （10 μmol L-1）在PNHFD和对照DMV神经元中诱导的内向电流相当，但高浓度（50 μmol L-1）在PNHFD神经元中诱导的电流更大。对于相相GABA拮抗剂gabazine （GBZ）、突触外GABA激动剂THIP、GABA转运阻滞剂nipecotic acid或胶质毒素氟乙酸，神经元的反应差异不明显，这表明PNHFD改变了抑制性传递，但没有改变GABA受体密度或功能、GABA摄取或突触强度的胶质调节。同样，在PNHFD大鼠脑干显微注射低剂量BIC（1‐10 pmol）和GBZ（0.01‐0.1 pmol）后，胃运动和张力的增加在PNHFD大鼠中没有变化，而高剂量BIC （25 pmol）诱导胃张力的增加明显大于对照组。这些研究表明，暴露于PNHFD会增加DMV神经元的强直性抑制，可能导致胃功能迷走神经控制失调。
BackgroundPrevious studies suggest an increased inhibition of dorsal motor nucleus of the vagus (DMV) neurons following exposure to a perinatal high fat diet (PNHFD); the underlying neural mechanisms, however, remain unknown. This study assessed the effects of PNHFD on inhibitory synaptic inputs to DMV neurons and the vagally dependent control of gastric tone and motility.MethodsWhole‐cell patch clamp recordings were made from DMV neurons in thin brainstem slices from Sprague‐Dawley rats fed either a control diet or HFD (14 or 60% kcal from fat, respectively) from embryonic day 13 onwards; gastric tone and motility were recorded in in vivo anesthetized rats.Key ResultsThe non‐selective GABAAantagonist, BIC (10 μmol L–1), induced comparable inward currents in PNHFD and control DMV neurons, but a larger current in PNHFD neurons at higher concentrations (50 μmol L–1). Differences were not apparent in neuronal responses to the phasic GABAAantagonist, gabazine (GBZ), the extrasynaptic GABAAagonist, THIP, the GABA transport blocker, nipecotic acid, or the gliotoxin, fluoroacetate, suggesting that PNHFD altered inhibitory transmission but not GABAAreceptor density or function, GABA uptake or glial modulation of synaptic strength. Similarly, the increase in gastric motility and tone following brainstem microinjection of low doses of BIC (1‐10 pmoles) and GBZ (0.01‐0.1 pmoles) were unchanged in PNHFD rats while higher doses of BIC (25 pmoles) induced a significantly larger increase in gastric tone compared to control.Conclusions and InferencesThese studies suggest that exposure to PNHFD increases the tonic inhibition of DMV neurons, possibly contributing to dysregulated vagal control of gastric functions.