M4毒蕈碱受体(MR)可能在运动协调中起作用。根据遗传背景和回交次数,以前的研究显示出不同的结果。然而,没有注意生物节律。
因此,我们分析了在完整动物中通过遥测获得的光/暗周期下的生物节律(活动,体温)在M4KO小鼠中使用ChronosFit软件在C57Bl6背景下生长。研究日常节律中基因敲除的纯作用对于通常在早晨测试药物的药理学/行为学研究尤其重要。
我们表明,M4KO小鼠的运动活动与野生型小鼠在光照期而在黑暗期(小鼠一天的活动部分)没有实质性差异,M4KO小鼠揭示了许多参数的生物节律变化。此外,这些差异是性别依赖性的,并且仅在女性中很明显。Mesor,白天和黑夜的区别,将女性KO与男性KO进行比较时,夜间价值增加了一倍或两倍。我们的体外放射自显影显示,M4MR比例在运动皮层(MOCx)中占24%,30%的体感皮层,纹状体的50%,69%的丘脑,膝关节间小叶(IGL)中占48%。室旁区的M4MR密度可以忽略不计,下丘脑后部,在视交叉上核。
我们得出结论,大脑结构如纹状体中M4MR的胆碱能信号传导,MOCx,并可能与IGL的重要参与显着控制运动活动的生物节律。动物活动在明暗阶段不同,在解释结果时应该考虑到这一点。
M4 muscarinic receptors (MR) presumably play a role in motor coordination. Previous studies have shown different results depending on genetic background and number of backcrosses. However, no attention has been given to biorhythms.
We therefore analyzed biorhythms under a light/dark cycle obtained telemetrically in intact animals (activity, body temperature) in M4 KO mice growth on the C57Bl6 background using ChronosFit software. Studying pure effects of gene knockout in daily rhythms is especially important knowledge for pharmacological/behavioral studies in which drugs are usually tested in the morning.
We show that M4 KO mice motor activity does not differ substantially from wild-type mice during light period while in the dark phase (mice active part of the day), the M4 KO mice reveal biorhythm changes in many parameters. Moreover, these differences are sex-dependent and are evident in females only. Mesor, night-day difference, and night value were doubled or tripled when comparing female KO versus male KO. Our in vitro autoradiography demonstrates that M4 MR proportion represents 24% in the motor cortex (MOCx), 30% in the somatosensory cortex, 50% in the striatum, 69% in the thalamus, and 48% in the intergeniculate leaflet (IGL). The M4 MR densities were negligible in the subparaventricular zone, the posterior hypothalamic area, and in the suprachiasmatic nuclei.
We conclude that cholinergic signaling at M4 MR in brain structures such as striatum, MOCx, and probably with the important participation of IGL significantly control motor activity biorhythm. Animal activity differs in the light and dark phases, which should be taken into consideration when interpreting the results.