目的:神经周围网(PNN)是中枢神经系统的特化细胞外基质(ECM)成分,经常积累在抑制性GABA能中间神经元的表面。虽然在包括阿尔茨海默病在内的神经系统疾病中观察到PNN的分布改变,精神分裂症和癫痫,它们的解剖分布在生理大脑成熟和衰老过程中也会发生变化。这种年龄依赖性的变化在实验上也与大脑成熟过程中的海马印迹形成有关。我们的目的是通过组织病理学评估成年和儿童颞叶癫痫(TLE)患者海马中的PNN与年龄匹配的死后对照受试者相比,并比较PNN相关变化与我们患者队列中观察到的记忆障碍。
方法:从欧洲癫痫脑库中检索到66个福尔马林固定和石蜡包埋的人海马组织标本。29例患者有组织病理学证实的海马硬化(HS),11例TLE患者无HS。使用针对聚集蛋白聚糖的抗体对PNN进行免疫组织化学可视化,并从海马亚区和下膜手动计数。
结果:在人类对照组和TLE患者中,PNN密度随年龄增加而增加。然而,与年龄匹配的对照组相比,所有HS患者的密度均显著较高.有趣的是,当海马PNN密度较高时,TLE患者表现出更好的记忆力(p<0.05)。
结论:我们的结果与人类海马中年龄依赖性ECM特化及其在癫痫状态下的早熟老化相一致。这些观察结果证实了最近的实验动物模型,也支持了PNN在人脑记忆形成中发挥作用的观点。
结论:“神经周围网”(PNN)是细胞外基质(ECM)的专门隔室,尤其是围绕哺乳动物大脑的高活性神经元。有证据表明PNN在记忆形成中起作用,大脑成熟,在一些疾病中,如阿尔茨海默病,精神分裂症或癫痫。在这项研究中,与对照组相比,我们调查了PNN在耐药局灶性癫痫患者中的作用.我们发现随着年龄的增长,更多的神经元被PNN包围。同样,所有癫痫患者,尤其是记忆能力较好的患者也有更多的PNN.这项研究引起了对在生理和病理生理条件下研究人脑中ECM分子的进一步兴趣。
OBJECTIVE: Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer\'s disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age-dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age-matched post-mortem control subjects and to compare PNN-related changes with memory impairment observed in our patient cohort.
METHODS: Sixty-six formalin-fixed and paraffin-embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty-nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum.
RESULTS: PNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age-matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p < 0.05).
CONCLUSIONS: Our results were compatible with age-dependent ECM specialization in the human hippocampus and its precocious aging in the epileptic condition. These observations confirm recent experimental animal models and also support the notion that PNN play a role in memory formation in the human brain.
CONCLUSIONS: \"Perineuronal nets\" (PNN) are a specialized compartment of the extracellular matrix (ECM), especially surrounding highly active neurons of the mammalian brain. There is evidence that PNN play a role in memory formation, brain maturation, and in some pathologies like Alzheimer\'s disease, schizophrenia or epilepsy. In this study, we investigated the role of PNN in patients suffering from drug-resistant focal epilepsy compared to controls. We found that with increasing age, more neurons are surrounded by PNN. Similarly, all epilepsy patients but especially patients with better memory performance also had more PNN. This study raises further interest in studying ECM molecules in the human brain under physiological and pathophysiological conditions.