背景:精神分裂症的发作与大脑发育的多个关键过程同时发生,例如抑制网络的成熟。其中一些过程被提议依赖于神经周网(PNN)的发展,一种专门的细胞外基质结构,优先围绕含有小白蛋白的GABA能中间神经元(PVIs)。PNN对于抑制性脑回路的产后经验依赖性成熟至关重要。PNN异常已被认为是SCZ的核心病理生理发现,与SCZ症状潜在的电路中断的广泛后果有关。
目标:这里,我们系统地评估了SCZ受试者的死后脑研究中的PNN密度。
方法:在3个在线数据库中进行系统搜索(PubMed,Embase,和Scopus),并对病例对照研究进行定性审查分析,报告SCZ受试者死后大脑中PNN密度。
结果:结果由7项研究组成,纳入最终分析。研究中研究的特定大脑区域各不相同,最关注的是背外侧前额叶皮质(DLPFC;3项研究)和杏仁核(2项研究)。SCZ中PNN密度降低的结果大多为阳性,7项研究中有6项报告显着减少,一项报告PNN密度降低的趋势。总的来说,组织处理方法是异质的。
结论:尽管研究很少,在SCZ中,PNN密度在不同的大脑区域一致降低。这些发现支持了在SCZ的病理生理学中PNN密度不足的证据。然而,更多研究,最好使用类似的方法学方法以及重复发现,是需要的。
BACKGROUND: The onset of schizophrenia is concurrent with multiple key processes of brain development, such as the maturation of inhibitory networks. Some of these processes are proposed to depend on the development of perineuronal nets (PNNs), a specialized extracellular matrix structure that surrounds preferentially
parvalbumin-containing GABAergic interneurons (PVIs). PNNs are fundamental to the postnatal experience-dependent maturation of inhibitory brain circuits. PNN abnormalities have been proposed as a core pathophysiological finding in SCZ, being linked to widespread consequences on circuit disruptions underlying SCZ symptoms.
OBJECTIVE: Here, we systematically evaluate PNN density in postmortem brain studies of subjects with SCZ.
METHODS: A systematic search in 3 online databases (PubMed, Embase, and Scopus) and qualitative review analysis of case-control studies reporting on PNN density in the postmortem brain of subjects with SCZ were performed.
RESULTS: Results consisted of 7 studies that were included in the final analysis. The specific brain regions investigated in the studies varied, with most attention given to the dorsolateral prefrontal cortex (DLPFC; 3 studies) and amygdala (2 studies). Findings were mostly positive for reduced PNN density in SCZ, with 6 of the 7 studies reporting significant reductions and one reporting a tendency towards reduced PNN density. Overall, tissue processing methodologies were heterogeneous.
CONCLUSIONS: Despite few studies, PNN density was consistently reduced in SCZ across different brain regions. These findings support evidence that implicates deficits in PNN density in the pathophysiology of SCZ. However, more studies, preferably using similar methodological approaches as well as replication of findings, are needed.