Mapping of STB/HAP1 Immunoreactivity in the Mouse Brainstem and its Relationships with Choline Acetyltransferase, with Special Emphasis on Cranial Nerve Motor and Preganglionic Autonomic Nuclei
Mapping of STB/HAP1 Immunoreactivity in the Mouse Brainstem and its Relationships with Choline Acetyltransferase, with Special Emphasis on Cranial Nerve Motor and Preganglionic Autonomic Nuclei
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DOI：
10.1016/j.neuroscience.2022.07.016
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发表时间：
2022-08-01
期刊：
影响因子：
3.3
通讯作者：
Shinoda，Koh
中科院分区：
文献类型：
--
作者：
Islam，Md Nabiul;Miyasato，Emi;Shinoda，Koh
亨廷顿蛋白相关蛋白1 （HAP1）是柱头体（STB）的核心成分，被认为是多种神经退行性疾病的神经保护相互作用因子。富含STB/HAP1免疫反应性的脑区通常免于细胞死亡，而STB/HAP1免疫反应性可忽略的脑区是主要的神经退行性靶点。最近，我们发现STB/HAP1在脊髓神经节前交感/副交感神经元中大量表达，而在脊髓运动神经元中缺失，这表明脊髓运动神经元更容易受到神经退行性疾病的影响。鉴于STB/HAP1的神经保护作用，阐明STB/HAP1在另一个主要的神经退行性靶点——脑干中的分布也是必要的。在此，我们检测了STB/HAP1在成年小鼠中脑、脑桥和延髓中的表达和详细的免疫组织化学分布及其与胆碱乙酰转移酶（ChAT）的关系。大量的STB/HAP1免疫反应神经元分布于导水管周围灰质、Edinger-Westphal核、中缝核、蓝斑核、桥脚被盖核、上/下流涎核和迷走神经背运动核。HAP1与ChAT（或Edinger-Westphal核中心突出人群的尿皮质素-1）的双标记免疫组化证实，STB/HAP1在副交感神经节前神经元中高度存在，但在整个脑干的颅神经运动核中完全不存在。这些结果表明，由于缺乏假定的STB/ hap1保护作用，颅神经运动核可能比表达STB/ hap1的脑干核更容易受到某些神经退行性应激，包括神经节前副交感神经核。我们的研究结果也为进一步阐明STB/HAP1在脑干中的生理/病理作用奠定了基础。
Huntingtin-associated protein 1 (HAP1) is a core component of stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for various neurodegenerative diseases. Brain regions rich in STB/HAP1 immunoreactivity are usually spared from cell death, whereas brain regions with negligible STB/HAP1 immunoreactivity are the major neurodegenerative targets. Recently, we have shown that STB/HAP1 is abundantly expressed in the spinal preganglionic sympathetic/parasympathetic neurons but absent in the motoneurons of spinal cord, indicating that spinal motoneurons are more vulnerable to neurodegenerative diseases. In light of STB/HAP1 neuroprotective effects, it is also essential to clarify the distribution of STB/HAP1 in another major neurodegenerative target, the brainstem. Here, we examined the expression and detailed immunohistochemical distribution of STB/HAP1 and its relationships with choline acetyltransferase (ChAT) in the midbrain, pons, and medulla oblongata of adult mice. Abundant STB/HAP1 immunoreactive neurons were disseminated in the periaqueductal gray, Edinger-Westphal nucleus, raphe nuclei, locus coeruleus, pedunculopontine tegmental nucleus, superior/inferior salivatory nucleus, and dorsal motor nucleus of vagus. Double-label immunohistochemistry of HAP1 with ChAT (or with urocortin-1 for Edinger-Westphal nucleus centrally projecting population) confirmed that STB/HAP1 was highly present in parasympathetic preganglionic neurons but utterly absent in cranial nerve motor nuclei throughout the brainstem. These results suggest that due to deficient putative STB/HAP1-protectivity, cranial nerve motor nuclei might be more vulnerable to certain neurodegenerative stresses than STB/HAP1-expressing brainstem nuclei, including preganglionic parasympathetic nuclei. Our current results also lay a basic foundation for future studies that seek to clarify the physiological/pathological roles of STB/HAP1 in the brainstem.