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自闭症中小脑篮状细胞和星状细胞的密度:浦肯野细胞发育后期丢失的证据。

Density of cerebellar basket and stellate cells in autism: evidence for a late developmental loss of Purkinje cells.

作者信息

Whitney Elizabeth R, Kemper Thomas L, Rosene Douglas L, Bauman Margaret L, Blatt Gene J

机构信息

Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02218-2526, USA.

出版信息

J Neurosci Res. 2009 Aug 1;87(10):2245-54. doi: 10.1002/jnr.22056.

Abstract

Alterations in the cerebellum have been described as a neuropathological feature of autism. Although numerous studies have focused on the Purkinje cell (PC), the projection neuron of the cerebellar cortex, PC function is critically dependent on their innervation by the GABAergic basket cells (BCs) and stellate cells (SCs) in the cerebellar molecular layer. The present study was designed to determine whether there are differences in the packing density of these inhibitory interneurons or whether the ratio of these interneurons to PCs differs in autistic and age-matched control brains. The GABAergic interneurons were identified by using immunohistochemistry for parvalbumin (PV) in serial sections from the posterior cerebellar lobe of six autistic and four control brains and counted using stereological principles. Prior PC counts in the same area on adjacent sections (Whitney et al., 2008) were available and were used to calculate the number of BCs and SCs per PC. In this sample of brains, no statistically significant difference was detected between the autistic and the control groups in the density of BCs or SCs (P = 0.44 and P = 0.84, respectively) or in the number of BCs or SCs per PC (P = 0.47 and P = 0.44, respectively). The preservation of BCs and SCs, in the presence of the reduced PC numbers as found in at least two, and possibly three, of these six autistic cases (Whitney et al., 2008) suggests that PCs were generated, migrated to their proper location in the PC layer, and subsequently died in the autistic cases that showed a reduction in PCs.

摘要

小脑的改变已被描述为自闭症的一种神经病理学特征。尽管众多研究聚焦于小脑皮质的投射神经元浦肯野细胞(PC),但PC的功能严重依赖于小脑分子层中γ-氨基丁酸能篮状细胞(BCs)和星状细胞(SCs)对其的神经支配。本研究旨在确定这些抑制性中间神经元的堆积密度在自闭症患者与年龄匹配的对照大脑中是否存在差异,或者这些中间神经元与PC的比例是否不同。通过对6例自闭症患者和4例对照大脑的小脑后叶连续切片进行小白蛋白(PV)免疫组织化学染色来识别γ-氨基丁酸能中间神经元,并运用体视学原理进行计数。之前在相邻切片的相同区域对PC进行的计数(Whitney等人,2008年)是可用的,并用于计算每个PC的BCs和SCs数量。在这个大脑样本中,自闭症组与对照组在BCs或SCs的密度(分别为P = 0.44和P = 0.84)或每个PC的BCs或SCs数量(分别为P = 0.47和P = 0.44)方面均未检测到统计学上的显著差异。在这6例自闭症患者中,至少有2例,可能有3例存在PC数量减少的情况下,BCs和SCs却得以保留,这表明在显示PC数量减少的自闭症病例中,PCs已经生成,迁移到PC层的适当位置,随后死亡。

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