Unite INSERM, U836-UJFG, GIN, France.
Int J Obes (Lond). 2012 Dec;36(12):1537-44. doi: 10.1038/ijo.2011.271. Epub 2012 Feb 21.
The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity.
Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8-10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation.
Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11-19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8 ± 4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded.
The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate.
作者提出了一种在第三脑室(V3)中插入靠近腹内侧下丘脑(VMH)的“漂浮”电极,以调节食物摄入量(FI)、体脂肪(BF)、体重(BW)和体重指数(BMI),作为肥胖治疗的一种潜在方法。
将 5 只成年食蟹猴通过立体定向手术植入 V3 紧邻 VMH 部位,植入 1 个深部脑刺激(DBS)电极。研究分为两个阶段:(a)急性 24 小时禁食试验:对禁食的灵长类动物施加不同的电刺激参数,以确定减少 FI 的最佳组合;(b)慢性 8 周刺激试验:分别以 130 Hz、80 Hz(最有效降低 FI 的频率)和 30 Hz 进行 3 个周期的脑室-VMH DBS 刺激,持续 8-10 周。在基线和每次刺激结束时测量 BMI、BW、BF 含量、皮褶厚度和激素。
急性 24 小时禁食试验:所有动物在 80 Hz 时 FI 均下降(11-19%,平均 15%)。慢性 8 周刺激试验:四只猴子中有三只在 80 Hz 时 BW 和 BMI 显著下降(平均 8±4.4%)。四只动物的皮下皮褶厚度在 80 Hz 时均减少,在 130 Hz 时略有增加。假手术猴保持稳定。未记录到明显的不良反应。
通过脑室途径刺激 VMH 区域可能会急性调节 FI,并在正常非人类灵长类动物中持续降低 BW 和脂肪量。