Neurophysiology Unit, Cardiac Electrophysiology Research, and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
J Endocrinol. 2021 Jan;248(1):59-74. doi: 10.1530/JOE-20-0439.
Exogenous treatment of a neurotensin receptor 1 (NTR1) agonist exerted the neuroprotection in an obese and Alzheimer's model. However, the effects of NTR1 modulation on peripheral/hippocampal impairment and cognitive deficit following sustained HFD consumption are poorly understood. Forty rats received a normal diet (ND) or HFD for 16 weeks. At week 13, the ND group received a vehicle (n = 8). Thirty-two HFD-fed group were randomized into four subgroups (n = 8/subgroup) with a vehicle, 1 mg/kg of NTR1 agonist, 1 mg/kg of NTR antagonist, and combined treatment (NTR1 agonist-NTR antagonist) for 2 weeks, s.c. injection. Then, the cognitive tests and peripheral/hippocampal parameters were determined. Our findings demonstrated that NTR1 activator reversed obesity and attenuated metabolic impairment in pre-diabetic rats. It also alleviated hippocampal pathologies and synaptic dysplasticity, leading to deceleration or prevention of cognitive impairment progression. Therefore, NTR1 activation would be a possible novel therapy to decelerate or prevent progression of neuropathology and cognitive impairment in the pre-diabetes.
外源性给予神经降压素受体 1（NTR1）激动剂可在肥胖和阿尔茨海默病模型中发挥神经保护作用。然而，NTR1 调节对持续高脂肪饮食（HFD）摄入后外周/海马损伤和认知缺陷的影响知之甚少。40 只大鼠接受正常饮食（ND）或 HFD 喂养 16 周。在第 13 周，ND 组给予载体（n = 8）。32 只 HFD 喂养组随机分为四组（n = 8/组），分别给予载体、1mg/kg NTR1 激动剂、1mg/kg NTR 拮抗剂和联合治疗（NTR1 激动剂-NTR 拮抗剂）2 周，皮下注射。然后测定认知测试和外周/海马参数。我们的研究结果表明，NTR1 激动剂逆转了糖尿病前期大鼠的肥胖和代谢损伤。它还减轻了海马病理学和突触发育不良，从而减缓或预防认知障碍的进展。因此，NTR1 激活可能是一种新的治疗方法，可以减缓或预防糖尿病前期神经病理学和认知障碍的进展。
