Pantazopoulos Harry, Berretta Sabina
Translational Neuroscience Laboratory, Mclean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
Translational Neuroscience Laboratory, Mclean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA.
Neural Plast. 2016;2016:9847696. doi: 10.1155/2016/9847696. Epub 2015 Dec 29.
Rapidly emerging evidence implicates perineuronal nets (PNNs) and extracellular matrix (ECM) molecules that compose or interact with PNNs, in the pathophysiology of several psychiatric disorders. Studies on schizophrenia, autism spectrum disorders, mood disorders, Alzheimer's disease, and epilepsy point to the involvement of ECM molecules such as chondroitin sulfate proteoglycans, Reelin, and matrix metalloproteases, as well as their cell surface receptors. In many of these disorders, PNN abnormalities have also been reported. In the context of the "quadripartite" synapse concept, that is, the functional unit composed of the pre- and postsynaptic terminals, glial processes, and ECM, and of the role that PNNs and ECM molecules play in regulating synaptic functions and plasticity, these findings resonate with one of the most well-replicated aspects of the pathology of psychiatric disorders, that is, synaptic abnormalities. Here we review the evidence for PNN/ECM-related pathology in these disorders, with particular emphasis on schizophrenia, and discuss the hypothesis that such pathology may significantly contribute to synaptic dysfunction.
迅速涌现的证据表明，神经元周围网（PNNs）以及构成PNNs或与PNNs相互作用的细胞外基质（ECM）分子，参与了多种精神疾病的病理生理过程。对精神分裂症、自闭症谱系障碍、情绪障碍、阿尔茨海默病和癫痫的研究表明，硫酸软骨素蛋白聚糖、Reelin和基质金属蛋白酶等ECM分子及其细胞表面受体参与其中。在许多这些疾病中，也有关于PNN异常的报道。在“四方”突触概念的背景下，即由突触前和突触后终末、神经胶质突起和ECM组成的功能单位，以及PNNs和ECM分子在调节突触功能和可塑性中所起的作用，这些发现与精神疾病病理学中最具重复性的方面之一，即突触异常相呼应。在此，我们综述了这些疾病中与PNN/ECM相关病理的证据，尤其着重于精神分裂症，并讨论了这种病理可能显著导致突触功能障碍的假说。
