Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Biomolecules. 2022 Mar 14;12(3):449. doi: 10.3390/biom12030449.
This study aimed to determine the effect of age on CVLM C1 neuron glucoregulatory proteins in the feeding pathway. Male Sprague Dawley rats aged 3 months and 24 months old were divided into two subgroups: the treatment group with 2-deoxy-d-glucose (2DG) and the control group. Rat brains were dissected to obtain the CVLM region of the brainstem. Western blot was used to determine protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK), and neuropeptide Y Y5 receptors (NPY5R) in CVLM samples. Immunofluorescence was used to determine TH-, AMPK-, and NPY5R-like immunoreactivities among other brain coronal sections. Results obtained denote a decrease in basal TH phosphorylation levels and AMPK proteins and an increase in TH proteins among aged CVLM neurons. Increases in the basal immunoreactivity of TH+, AMPK+, NPY5R+, TH+/AMPK+, and TH+/NPY5R+ were also observed among old rats. Young treatment-group rats saw a decrease in TH phosphorylation and AMPK proteins following 2DG administration, while an increase in AMPK phosphorylation and a decrease in TH proteins were found among the old-treatment-group rats. These findings suggest the participation of CVLM C1 neurons in counter-regulatory responses among young and old rats. Altering protein changes in aged CVLM C1 neurons may attenuate responses to glucoprivation, thus explaining the decline in food intake among the elderly.
本研究旨在探讨年龄对摄食通路上 CVLM C1 神经元糖调节蛋白的影响。雄性 Sprague Dawley 大鼠分为 3 月龄和 24 月龄 2 组，每组再分为 2-脱氧-D-葡萄糖（2DG）处理组和对照组。取大鼠脑，分离脑桥 CVLM 区。Western blot 检测 CVLM 样本中酪氨酸羟化酶（TH）、丝氨酸 40 磷酸化 TH（pSer40TH）、AMP 激活蛋白激酶（AMPK）、磷酸化 AMPK（phospho AMPK）和神经肽 Y Y5 受体（NPY5R）的蛋白表达；免疫荧光检测其他脑冠状切片中 TH、AMPK 和 NPY5R 样免疫反应性。结果显示，衰老 CVLM 神经元的基础 TH 磷酸化水平和 AMPK 蛋白降低，TH 蛋白增加。老年大鼠基础 TH+、AMPK+、NPY5R+、TH+/AMPK+和 TH+/NPY5R+的免疫反应性也增加。年轻治疗组大鼠给予 2DG 后 TH 磷酸化和 AMPK 蛋白减少，而老年治疗组大鼠 AMPK 磷酸化增加，TH 蛋白减少。这些发现提示 CVLM C1 神经元参与了年轻和老年大鼠的代偿性反应。改变衰老 CVLM C1 神经元的蛋白变化可能会减弱对糖剥夺的反应，从而解释老年人食欲下降的原因。
