Hermann Heike, Lutz Beat
Group Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany.
Neurosci Lett. 2005 Feb 25;375(1):13-8. doi: 10.1016/j.neulet.2004.10.080. Epub 2004 Dec 10.
The high abundance of the cannabinoid receptor type 1 (CB1) in the brain and the discovery of its endogenous ligands possessing neuromodulatory activities suggest an important potential of the endocannabinoid system to influence the functions of other receptor systems in the brain, including the corticotropin releasing hormone (CRH) system. Several studies evidenced a cross-talk between these two receptor systems. In trying to detail functional interactions between CB1 and the CRH receptor type 1 (CRHR1), we performed double-label-in situ hybridisation on mouse forebrain sections to localise the transcripts encoding the two receptors at a cellular level. Colocalisation of both receptor mRNAs was only detected in low CB1-expressing cells, which are mainly principal projecting neurons, whereas high CB1-expressing cells, which are considered to be mostly GABAergic did not contain mRNA encoding CRHR1. CB1 is differentially coexpressed with CRHR1 in olfactory regions, in several cortical and limbic structures, and in some hypothalamic and thalamic nuclei. These observations suggest a complex mechanism underlying the mutual interrelation and modulation of the two receptor systems. In particular, high levels of coexpressing cells in cortical and limbic areas may relate to cognitive functions, such as working memory, emotional and declarative learning. Colocalisation of CB1 and CRHR1 in hypothalamic regions strongly suggests functional interactions regarding the neuroendocrine homeostasis, including feeding behaviour.
大脑中1型大麻素受体（CB1）的高丰度以及其具有神经调节活性的内源性配体的发现表明，内源性大麻素系统在影响大脑中其他受体系统功能方面具有重要潜力，包括促肾上腺皮质激素释放激素（CRH）系统。多项研究证明了这两种受体系统之间存在相互作用。为了详细研究CB1与1型促肾上腺皮质激素释放激素受体（CRHR1）之间的功能相互作用，我们对小鼠前脑切片进行了双标记原位杂交，以在细胞水平上定位编码这两种受体的转录本。仅在低表达CB1的细胞中检测到两种受体mRNA的共定位，这些细胞主要是主要投射神经元，而高表达CB1的细胞（大多被认为是γ-氨基丁酸能神经元）不含编码CRHR1的mRNA。在嗅觉区域、几个皮质和边缘结构以及一些下丘脑和丘脑核中，CB1与CRHR1呈差异共表达。这些观察结果表明，这两种受体系统相互关联和调节的机制很复杂。特别是，皮质和边缘区域中高表达共定位的细胞可能与认知功能有关，如工作记忆、情感和陈述性学习。CB1和CRHR1在下丘脑区域的共定位强烈表明，它们在神经内分泌稳态（包括进食行为）方面存在功能相互作用。
