Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia.
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia.
Exp Gerontol. 2020 Jan;129:110779. doi: 10.1016/j.exger.2019.110779. Epub 2019 Nov 6.
Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function.
This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response.
Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR.
This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased.
These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.
老年人可能会出现厌食症。延髓腹外侧区（RVLM）中的头端 C1（rC1）儿茶酚胺能神经元最近被发现其在摄食控制中的作用。众所周知，这些神经元调节心血管功能。
本研究旨在确定年龄对介导摄食反应的头端 C1（rC1）神经元功能的影响。
雄性 Sprague Dawley 大鼠分别在 3 个月（n=22）和 24 个月（n=22）龄时使用，并进一步分为两组；1）2-脱氧-D-葡萄糖（2DG）处理组和 2）载体组。使用酶联免疫吸附试验（ELISA）分析胆囊收缩素（CCK）、胃饥饿素和瘦素等摄食激素。小心解剖大鼠脑以获得延髓 RVLM 区。进一步分析用于确定与摄食途径相关的 RVLM 中的蛋白质和基因水平。通过 Western blot 测定酪氨酸羟化酶（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。通过实时 PCR 测定 TH、AMPK 和 NPY 基因的表达。
本研究表明，2DG 给药后年轻和老年大鼠的血糖水平升高。基础时老年大鼠的血浆 CCK-8 浓度较高，年轻大鼠 2DG 给药后增加，而瘦素和胃饥饿素无变化。老年大鼠的 TH 和 AMPK mRNA 水平较高。糖剥夺降低了年轻大鼠的 AMPK mRNA 水平，并降低了老年大鼠的 TH mRNA 水平。老年 rC1 神经元的 NPY5R 蛋白水平较高。糖剥夺后，rC1 神经元在年轻大鼠中 AMPK 磷酸化水平增加，在老年大鼠中 TH 磷酸化水平增加，在年轻和老年大鼠中产生了不同的分子变化。
这些发现表明，rC1 神经元的葡萄糖对抗反应至少有助于年轻和老年大鼠应对糖剥夺的能力。rC1 神经元内的年龄诱导的分子变化可能会减弱糖剥夺反应。这种情况可能解释了老年人摄食反应受损的原因。
