PrPC基因敲除小鼠下丘脑-垂体-肾上腺轴失调
Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice.
作者信息
Sanchez-Alavez Manuel, Criado José R, Klein Izabella, Moroncini Gianluca, Conti Bruno
机构信息
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
出版信息
Neuroreport. 2008 Oct 8;19(15):1473-7. doi: 10.1097/WNR.0b013e32830f1e90.
As manifestations of prion diseases include disturbances of hypothalamic and pituitary functions, we tested the hypothesis that the cellular prion protein (PrPC) has a role as modulator of the hypothalamic-pituitary-adrenal axis. The level of corticosterone and adrenocorticotropic hormone were compared in PrPC null (PrP 0/0) and wild-type (PrP+/+) mice. PrP 0/0 showed hypercorticism during the dark part of day. After acute stress, corticosterone and adrenocorticotropic hormone increased similarly in PrP+/+ and PrP 0/0 mice. Adrenocorticotropic hormone, however, remained elevated in PrP+/+ 0/0 mice at corticosterone levels that are inhibitory in PrP mice. Pretreatment with corticosterone or dexamethasone inhibited stress-induced elevation of adrenocorticotropic hormone in PrP+/+ but not in PrP 0/0 mice. Thus, PrPC may play a role in the negative feedback regulation of axis.
由于朊病毒疾病的表现包括下丘脑和垂体功能紊乱，我们检验了细胞朊蛋白（PrPC）作为下丘脑-垂体-肾上腺轴调节因子的假说。比较了PrPC基因敲除（PrP 0/0）小鼠和野生型（PrP+/+）小鼠的皮质酮和促肾上腺皮质激素水平。PrP 0/0小鼠在白天的黑暗时段表现出高皮质醇血症。急性应激后，PrP+/+和PrP 0/0小鼠的皮质酮和促肾上腺皮质激素升高情况相似。然而，在PrP+/+小鼠中，皮质酮水平对促肾上腺皮质激素有抑制作用，但在PrP 0/0小鼠中，促肾上腺皮质激素仍保持升高。用皮质酮或地塞米松预处理可抑制PrP+/+小鼠应激诱导的促肾上腺皮质激素升高，但对PrP 0/0小鼠无效。因此，PrPC可能在该轴的负反馈调节中发挥作用。
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