Background

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.

Objective

This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response.

Method

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.

Results

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.

Conclusion

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.

中文翻译：

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年龄对进食反应的影响：着重于鼻端C1神经元及其糖调节蛋白。

背景

老年人可能会出现衰老厌食症。最近发现了在延髓腹侧延髓（RVLM）中的延髓C1（rC1）儿茶酚胺能神经元在控制食物摄入中的作用。众所周知，这些神经元调节心血管功能。

客观的

这项研究旨在确定年龄对介导进食反应的延髓性C1（rC1）神经元功能的影响。

方法

使用3月龄（n  = 22）和24月龄（n = 22）的雄性Sprague Dawley大鼠，并将其进一步分为两个亚组。1）治疗组与2-脱氧d-葡萄糖（2DG）和2）媒介物组。使用酶联免疫吸附测定（ELISA）分析了诸如胆囊收缩素（CCK），生长素释放肽和瘦素等饲料激素。仔细解剖大鼠脑以获得脑干RVLM区域。进行了进一步的分析以确定与进食途径相关的RVLM中的蛋白质和基因的水平。通过蛋白质印迹法测定酪氨酸羟化酶（TH），丝氨酸40处的磷酸化TH（pSer40TH），AMP激活的蛋白激酶（AMPK），磷酸化的AMPK（磷酸化AMPK）和神经肽Y Y5受体（NPY5R）的蛋白表达。通过实时PCR确定TH，AMPK和NPY基因的表达。

结果

这项研究表明，服用2DG后，年轻和老年大鼠的血糖水平均升高。在基础大鼠中，老年大鼠血浆CCK-8浓度较高，在幼鼠中随着2DG的使用，血浆CCK-8浓度升高，但是瘦素和生长素释放肽却没有变化。老年大鼠显示较高的TH和较低的AMPK mRNA水平。糖剥夺降低了幼鼠的AMPK mRNA水平，并降低了老鼠的TH mRNA水平。老年rC1神经元显示较高的NPY5R蛋白水平。糖缺乏后，rC1神经元随着年龄的增长产生明显的分子变化，其中年轻大鼠的AMPK磷酸化水平升高，而老年大鼠的TH磷酸化水平升高。

结论

这些发现表明，至少由rC1神经元引起的葡萄糖逆调节反应有助于幼小和老年大鼠应对糖缺乏的能力。rC1神经元内的年龄诱导的分子变化可能会减弱糖皮质激素反应。这种情况可以解释老年人进食反应的损害。