Losing the sugar coating: potential impact of perineuronal net abnormalities on interneurons in schizophrenia.
Losing the sugar coating: potential impact of perineuronal net abnormalities on interneurons in schizophrenia.
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DOI：
10.1016/j.schres.2014.12.040
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发表时间：
2015-09
影响因子：
4.5
通讯作者：
Batzianouli ET
中科院分区：
文献类型：
--
作者：
Berretta S;Pantazopoulos H;Markota M;Brown C;Batzianouli ET
精神分裂症患者的神经元周围神经网络（PNNs）有明显的改变。特别地，在杏仁核、内嗅皮层和前额叶皮层中已经检测到PNN的减少。这些专门的细胞外基质（ECM）聚集体的形成在出生后的发展，其功能和协会与不同的群体的GABA能中间神经元，承担精神分裂症的病理生理学有很大的相关性。PNN在出生后发育的后期阶段以经验依赖的方式逐渐成熟，与精神分裂症的前驱期/发病年龄重叠。在整个成年期，PNN调节神经元的特性，包括突触重塑，细胞膜区室化和随后的谷氨酸受体和钙通道的调节，以及对氧化应激的敏感性。在本文中，我们讨论的证据PNN异常精神分裂症，潜在的功能影响，这种异常的抑制电路，反过来，认知和情绪处理。我们将这些考虑与最近的遗传研究结果相结合，这些研究结果表明精神分裂症的遗传易感性与编码PNN组分、基质调节分子和免疫系统因子的基因相关。值得注意的是，PNN的组成是动态调节的因素，如恐惧，奖励，压力和免疫反应。这种调节通过基质金属蛋白酶家族发生，其切割ECM组分，改变其功能并影响可塑性。几种金属蛋白酶已被认为是精神分裂症的易感因素。我们推测，PNN重塑的生理过程可能会被破坏精神分裂症作为一个结果之间的相互作用基质重塑过程和免疫系统失调。反过来，这些机制可能导致GABA能神经元功能障碍。
Perineuronal nets (PNNs) were shown to be markedly altered in subjects with schizophrenia. In particular, decreases of PNNs have been detected in the amygdala, entorhinal cortex and prefrontal cortex. The formation of these specialized extracellular matrix (ECM) aggregates during postnatal development, their functions and association with distinct populations of GABAergic interneurons, bear great relevance to the pathophysiology of schizophrenia. PNNs gradually mature in an experience-dependent manner during late stages of postnatal development, overlapping with the prodromal period/age of onset of schizophrenia. Throughout adulthood, PNNs regulate neuronal properties, including synaptic remodeling, cell membrane compartmentalization and subsequent regulation of glutamate receptors and calcium channels, and susceptibility to oxidative stress. With the present paper, we discuss evidence for PNN abnormalities in schizophrenia, the potential functional impact of such abnormalities on inhibitory circuits and, in turn, cognitive and emotion processing. We integrate these considerations with results from recent genetic studies showing genetic susceptibility for schizophrenia associated with genes encoding for PNN components, matrix-regulating molecules and immune system factors. Notably, the composition of PNNs is regulated dynamically in response to factors such as fear, reward, stress, and immune response. This regulation occurs through families of matrix metalloproteinases that cleave ECM components, altering their functions and affecting plasticity. Several metalloproteinases have been proposed as vulnerability factors for schizophrenia. We speculate that the physiological process of PNN remodeling may be disrupted in schizophrenia as a result of interactions between matrix remodeling processes and immune system dysregulation. In turn, these mechanisms may contribute to dysfunction of GABAergic neurons.