Benarroch Eduardo E, Schmeichel Ann M, Sandroni Paola, Low Phillip A, Parisi Joseph E
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Brain. 2006 Oct;129(Pt 10):2688-96. doi: 10.1093/brain/awl109. Epub 2006 May 2.
We sought to determine whether there is differential involvement of different groups of hypothalamic arginine-vasopressin (AVP) synthesizing neurons in multiple system atrophy (MSA). Hypothalamus was obtained from five subjects with clinical diagnosis of MSA confirmed neuropathologically and five age-matched controls. Sections were immunostained for AVP, and cells with visible nuclei were counted in the posterior portion of the paraventricular nucleus (PVNp), supraoptic nucleus (SON), magnocellular PVN and suprachiasmatic nucleus (SCN). Sections of the hypothalamus and medulla were also immunostained for tyrosine hydroxylase (TH). There was a significant loss of AVP neurons in the PVNp in MSA compared with controls (17 +/- 3 versus 59 +/- 10 cells/section, P < 0.01). There was preservation of AVP- and TH-immunoreactive neurons in the SON and magnocellular PVN in all MSA cases. In contrast, there was marked depletion of TH-immunoreactive fibres innervating these magnocellular AVP neurons, coincident with a loss of neurons in the A1 area (6 +/- 1 versus 13 +/- 1 cells/section, P < 0.01). There was loss of AVP neurons in the SCN in MSA compared with control cases (14 +/- 3 versus 71 +/- 16 cells/section, P < 0.02). Our results indicate that, in MSA, loss of AVP neurons in the PVNp may contribute to sympathetic failure, whereas loss of catecholaminergic input from the brainstem to the magnocellular AVP neurons may contribute to impaired AVP secretion in response to orthostatic stress. Loss of AVP neurons in the SCN may contribute to impaired circadian regulation of endocrine and autonomic functions.
我们试图确定在多系统萎缩（MSA）中，不同组的下丘脑精氨酸加压素（AVP）合成神经元是否存在差异受累情况。下丘脑取自5例经神经病理学确诊为MSA的患者以及5例年龄匹配的对照者。切片进行AVP免疫染色，并对室旁核后部（PVNp）、视上核（SON）、大细胞性室旁核和视交叉上核（SCN）中可见细胞核的细胞进行计数。下丘脑和延髓切片也进行酪氨酸羟化酶（TH）免疫染色。与对照组相比，MSA患者PVNp中的AVP神经元显著减少（17±3个/切片 vs 59±10个/切片，P<0.01）。在所有MSA病例中，SON和大细胞性室旁核中的AVP和TH免疫反应性神经元均得以保留。相比之下，支配这些大细胞性AVP神经元的TH免疫反应性纤维明显减少，同时A1区的神经元也减少（6±1个/切片 vs 13±1个/切片，P<0.01）。与对照病例相比，MSA患者SCN中的AVP神经元减少（14±3个/切片 vs 71±16个/切片，P<0.02）。我们的结果表明，在MSA中，PVNp中AVP神经元的丧失可能导致交感神经功能衰竭，而脑干向大细胞性AVP神经元的儿茶酚胺能输入丧失可能导致对直立性应激的AVP分泌受损。SCN中AVP神经元的丧失可能导致内分泌和自主功能的昼夜节律调节受损。
