小鼠蓝斑中含有α1肾上腺素能受体元件的定位和神经化学特性。

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-09-28 DOI:10.1016/j.jchemneu.2023.102343
Zachary N.M. Luyo , Abigail B. Lawrence , Theodore G. Stathopoulos , Darlene A. Mitrano
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引用次数: 0

摘要

蓝斑(LC)是大脑中去甲肾上腺素(NE)的主要来源,并投射到与学习和记忆、奖励、唤醒、注意力和与压力相关的自主功能有关的区域。有三种类型的肾上腺素能受体对NE有反应:α1-、α2-和β肾上腺素能受体。然而,先前的行为研究表明,α1肾上腺素能受体(α1AR)存在于LC中,结果相互矛盾。例如,研究表明,LC中的α1AR参与刺激内侧前脑束的一些动机作用,而α1AR拮抗剂特拉唑嗪可降低这种作用。另一项研究表明,在新奇诱导的行为激活过程中,α1AR拮抗剂哌唑嗪降低了已知含有运动α1AR的大脑区域的c-fos表达,但LC除外,在LC中c-fos表达增强。尽管新的研究描述了LC中神经元的更特异性连接,以及肾上腺素能受体的一些作用,但α1ARs尚未在亚细胞水平上定位。因此,为了更好地了解上述研究,我们在电子显微镜(EM)水平上使用免疫组织化学来确定LC中哪些神经元或神经胶质元件表达α1AR。根据先前在腹侧导水管周围灰质的研究,我们假设α1AR主要在突触前的轴突终末发现,可能在神经胶质细胞中发现。EM的单标记免疫组织化学显示,约40%的含有α1AR的标记元件是神经胶质元件,而约50%的标记神经元元件是LC中的轴突终末或小的无髓鞘轴突。双标记免疫组织化学发现,α1AR在GFAP标记的星形胶质细胞中表达,在GABA能和谷氨酸能轴突终末,以及在一部分α1AR树突中,与酪氨酸羟化酶(TH,去甲肾上腺素能神经元的标志物)共定位。这项研究揭示了NE和药物直接或间接作用于LC中α1ARs的影响的神经解剖学框架。
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Localization and neurochemical identity of alpha1-adrenergic receptor-containing elements in the mouse locus coeruleus

The locus coeruleus (LC) is the major source for norepinephrine (NE) in the brain and projects to areas involved in learning and memory, reward, arousal, attention, and autonomic functions related to stress. There are three types of adrenergic receptors that respond to NE: alpha1-, alpha2-, and beta-adrenergic receptors. Previous behavioral studies have shown the alpha1-adrenergic receptor (α1AR) to be present in the LC, however, with conflicting results. For example, it was shown that α1ARs in the LC are involved in some of the motivational effects of stimulation of the medial forebrain bundle, which was reduced by α1AR antagonist terazosin. Another study showed that during novelty-induced behavioral activation, the α1AR antagonist prazosin reduced c-fos expression in brain regions known to contain motoric α1ARs, except for the LC, where c-fos expression was enhanced. Despite new research delineating more specific connectivity of the neurons in the LC, and some roles of the adrenergic receptors, the α1ARs have not been localized at the subcellular level. Therefore, in order to gain a greater understanding of the aforementioned studies, we used immunohistochemistry at the electron microscopic (EM) level to determine which neuronal or glial elements in the LC express the α1AR. We hypothesized, based on previous work in the ventral periaqueductal gray area, that the α1AR would be found mainly presynaptically in axon terminals, and possibly in glial elements. Single labeling immunohistochemistry at the EM revealed that about 40% of labeled elements that contained the α1AR were glial elements, while approximately 50% of the labeled neuronal elements were axon terminals or small unmyelinated axons in the LC. Double labeling immunohistochemistry found the α1AR expressed in GFAP-labeled astrocytes, in both GABAergic and glutamatergic axon terminals, and in a portion of the α1AR dendrites, colocalized with tyrosine hydroxylase (TH, a marker for noradrenergic neurons). This study sheds light on the neuroanatomical framework underlying the effects of NE and pharmaceuticals acting directly or indirectly on α1ARs in the LC.

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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
期刊最新文献
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