在新一期《美国科学院院报》上的一项研究表明,母性照顾可能通过一个大脑受体影响焦虑和体重。神经递质神经肽Y帮助控制哺乳动物的焦虑、食欲和能量平衡;然而把小鼠大脑的为这种神经递质的受体编码的基因*去除似乎几乎不会影响到生理。
为了进一步探索这种受体对焦虑和体重的影响,Carola Eva及其同事改造了小鼠,让它的这种受体可以在大脑的边缘系统选择性地关闭-边缘系统帮助控制情绪和焦虑。这组作者报告说,这种改造后的小鼠更加焦虑,拥有的脂肪组织更少,而且体重比对照小鼠更低,但是只有在这些小鼠被一种已知能够提供细致的母性照顾,其标志是积极的弓背看护行为、在幼崽身边蹲下的次数增加,以及个人梳理毛皮和筑巢的活动减少,这样的育儿鼠品种抚养的情况下才会出现这种情况。当这些经过改造的小鼠幼崽被另一种已知母性照顾较少的小鼠品种养育的时候,它们几乎没有表现出焦虑和体重方面的明显效应,这提示边缘系统中的这种受体的制造取决于母性照顾。这组作者说,这些发现提示母性照顾可能通过神经肽Y及其受体控制焦虑和能量平衡。
doi:10.1073/pnas.1109468108
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Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care
Ilaria Bertocchi, Alessandra Oberto, Angela Longo, Paolo Mele, Marianna Sabettab, Alessandro Bartolomucci, Paola Palanzad, Rolf Sprengele, Carola Eva
Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1rrfb). Npy1rrfb mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1rrfb mutants also had a hyperactive hypothalamic-pituitary-adrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1rrfb and Npy1r2lox mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis.