Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (AL, PM, IB, AO, CE), Orbassano (Turin); Department of Neuroscience (AL, PM, IB, AO, CE).
Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (AL, PM, IB, AO, CE), Orbassano (Turin); Neuroscience Institute of Turin (AO, CE); Department of Neuroscience (AL, PM, IB, AO, CE).
Biol Psychiatry. 2014 Dec 1;76(11):840-9. doi: 10.1016/j.biopsych.2014.01.009. Epub 2014 Jan 24.
The Y1 receptor (Y1R) and Y5 receptor (Y5R) for neuropeptide Y share similar actions in the regulation of anxiety. Previously demonstrated that conditional removal of the Y1R during postnatal development in the forebrain excitatory neurons leads to higher anxiety, increased hypothalamus-pituitary-adrenocortical axis activity, and decreased body growth rate in male mice raised by foster mothers that exhibit high levels of maternal care. In the present study, we used the same conditional system to analyze the specific contribution to emotional behavior and stress response of the Y1R coexpressed with the Y5R.
Using the Cre-loxP recombination system, we investigated anxious behavior, spatial memory, and metabolic functions of conditional knockout mice in which the inactivation of the Npy1r gene was induced in the Y5Rs expressing neurons of juvenile mice (Npy1r(Y5R-/-) ).
Npy1r(Y5R-/-) mice show increased anxiety-related behavior but no changes in hypothalamus-pituitary-adrenocortical axis activity or in body weight growth, independently of gender and mouse strain used as foster mothers. Also, Npy1r(Y5R-/-) mice of both genders display increased spatial reference memory in the Morris water maze test.
The results suggest that neuropeptide Y Y1R differentially expressed in the limbic system regulates anxiety and stress responses via distinct neurochemical circuits. In addition, we provide the first experimental genetic evidence that the Y1Rs coexpressed with the Y5R are involved in retention of spatial memory in male and female mice.
神经肽 Y 的 Y1 受体（Y1R）和 Y5 受体（Y5R）在调节焦虑方面具有相似的作用。先前的研究表明，在大脑前兴奋性神经元的出生后发育过程中条件性去除 Y1R 会导致雄性小鼠焦虑增加、下丘脑-垂体-肾上腺轴活性增加和由表现出高水平母性关怀的寄养母亲抚养的小鼠的生长速度减慢。在本研究中，我们使用相同的条件性系统来分析与 Y5R 共表达的 Y1R 对情绪行为和应激反应的特定贡献。
使用 Cre-loxP 重组系统，我们研究了条件性敲除小鼠的焦虑行为、空间记忆和代谢功能，其中 Npy1r 基因的失活是在幼年小鼠的 Y5R 表达神经元中诱导的（Npy1r(Y5R-/-)）。
Npy1r(Y5R-/-) 小鼠表现出增加的焦虑相关行为，但下丘脑-垂体-肾上腺轴活性或体重增长没有变化，与用作寄养母亲的性别和小鼠品系无关。此外，Npy1r(Y5R-/-) 雌雄小鼠在 Morris 水迷宫测试中均显示出空间参考记忆增加。
这些结果表明，神经肽 Y Y1R 在边缘系统中的差异表达通过不同的神经化学回路调节焦虑和应激反应。此外，我们提供了第一个实验遗传证据，表明与 Y5R 共表达的 Y1R 参与了雄性和雌性小鼠的空间记忆保留。
