Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.
Neurogastroenterol Motil. 2018 Jan;30(1). doi: 10.1111/nmo.13150. Epub 2017 Aug 1.
Previous 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.
Whole-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.
The non-selective GABA antagonist, BIC (10 μmol L ), induced comparable inward currents in PNHFD and control DMV neurons, but a larger current in PNHFD neurons at higher concentrations (50 μmol L ). Differences were not apparent in neuronal responses to the phasic GABA antagonist, gabazine (GBZ), the extrasynaptic GABA agonist, THIP, the GABA transport blocker, nipecotic acid, or the gliotoxin, fluoroacetate, suggesting that PNHFD altered inhibitory transmission but not GABA receptor 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.
These studies suggest that exposure to PNHFD increases the tonic inhibition of DMV neurons, possibly contributing to dysregulated vagal control of gastric functions.
先前的研究表明，在接触围产期高脂肪饮食（PNHFD）后，背侧迷走神经运动核（DMV）神经元的抑制作用增强；然而，潜在的神经机制尚不清楚。本研究评估了 PNHFD 对 DMV 神经元抑制性突触传入以及迷走神经依赖性胃张力和运动的影响。
在胚胎第 13 天起用对照饮食或 HFD（分别为 14%或 60%来自脂肪的卡路里）喂养 Sprague-Dawley 大鼠后，从薄脑切片中进行 DMV 神经元的全细胞膜片钳记录；在麻醉的体内大鼠中记录胃张力和运动。
非选择性 GABA 拮抗剂 BIC（10 μmol·L）在 PNHFD 和对照 DMV 神经元中诱导出相当的内向电流，但在较高浓度（50 μmol·L）下在 PNHFD 神经元中诱导出更大的电流。在神经元对脉冲 GABA 拮抗剂gabazine（GBZ）、细胞外 GABA 激动剂 THIP、GABA 转运阻断剂 nipecotic 酸或神经毒素 fluoroacetate 的反应中没有差异，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 摄取或胶质调制突触强度。同样，在 PNHFD 大鼠中，脑桥内微量注射低剂量 BIC（1-10 pmoles）和 GBZ（0.01-0.1 pmoles）后，胃动力和张力增加不变，而较高剂量的 BIC（25 pmoles）引起胃张力的增加明显大于对照。
这些研究表明，暴露于 PNHFD 会增加 DMV 神经元的紧张性抑制，可能导致迷走神经对胃功能的调节失调。
