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在新一期《美國(guó)科學(xué)院院報(bào)》上的一項(xiàng)研究表明，母性照顧可能通過(guò)一個(gè)大腦受體影響焦慮和體重。神經(jīng)遞質(zhì)神經(jīng)肽Y幫助控制哺乳動(dòng)物的焦慮、食欲和能量平衡；然而把小鼠大腦的為這種神經(jīng)遞質(zhì)的受體編碼的基因*去除似乎幾乎不會(huì)影響到生理。
為了進(jìn)一步探索這種受體對(duì)焦慮和體重的影響，Carola Eva及其同事改造了小鼠，讓它的這種受體可以在大腦的邊緣系統(tǒng)選擇性地關(guān)閉-邊緣系統(tǒng)幫助控制情緒和焦慮。這組作者報(bào)告說(shuō)，這種改造后的小鼠更加焦慮，擁有的脂肪組織更少，而且體重比對(duì)照小鼠更低，但是只有在這些小鼠被一種已知能夠提供細(xì)致的母性照顧，其標(biāo)志是積極的弓背看護(hù)行為、在幼崽身邊蹲下的次數(shù)增加，以及個(gè)人梳理毛皮和筑巢的活動(dòng)減少，這樣的育兒鼠品種撫養(yǎng)的情況下才會(huì)出現(xiàn)這種情況。當(dāng)這些經(jīng)過(guò)改造的小鼠幼崽被另一種已知母性照顧較少的小鼠品種養(yǎng)育的時(shí)候，它們幾乎沒(méi)有表現(xiàn)出焦慮和體重方面的明顯效應(yīng)，這提示邊緣系統(tǒng)中的這種受體的制造取決于母性照顧。這組作者說(shuō)，這些發(fā)現(xiàn)提示母性照顧可能通過(guò)神經(jīng)肽Y及其受體控制焦慮和能量平衡。
doi:10.1073/pnas.1109468108
PMC:
PMID:
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.
