Rački Valentino, Petrić Daniela, Kučić Natalia, Gržeta Nika, Jurdana Kristina, Rončević-Gržeta Ika
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
Clinic of Psychiatry, University Hospital Clinic Rijeka, Croatia.
Med Hypotheses. 2016 Mar;88:18-21. doi: 10.1016/j.mehy.2015.12.021. Epub 2016 Jan 9.
Cortical gray matter loss in schizophrenia remains a great therapeutic difficulty. Each psychotic episode causes irreversible cortical gray matter loss, that causes the patients to never regain their previous state of functioning. Microglial cells are part of the innate immune system and their functions, among others, include phagocytosis and release of neurotrophic factors. They have a key impact on developmental and plasticity-induced removal of neuronal precursors, live-but-stressed neurons and synapses, while also stimulating synaptic growth and development. We hypothesize that microglia are the culprit for the cortical gray matter loss in schizophrenia through abnormal synaptic pruning, phagocytosis of stressed neurons and lacking neurotrophic factor release. Furthermore, we propose a research that could validate the hypotheses using serum samples of first-episode early-onset patients. By measuring the serum levels of milk fat globule-EGF factor 8 (MFG-E8), subcomponent in the classical pathway of complement activation (C1q), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and interleukin-10 (IL-10), we could gain an insight into the state of microglial activation during various stages of the disease. If this hypothesis is valid, new targeted drugs could be developed in order to reduce the deterioration of cortical gray matter, thereby possibly improving negative symptoms and cognitive deficits.
精神分裂症中的皮质灰质损失仍然是一个巨大的治疗难题。每次精神病发作都会导致不可逆的皮质灰质损失，使患者永远无法恢复到以前的功能状态。小胶质细胞是先天免疫系统的一部分，其功能包括吞噬作用和神经营养因子的释放等。它们对发育和可塑性诱导的神经元前体、存活但应激的神经元和突触的清除具有关键影响，同时也刺激突触的生长和发育。我们假设小胶质细胞是精神分裂症中皮质灰质损失的罪魁祸首，其通过异常的突触修剪、应激神经元的吞噬作用以及神经营养因子释放的缺乏导致这种损失。此外，我们提出了一项研究，该研究可以使用首发早发患者的血清样本验证这些假设。通过测量乳脂肪球表皮生长因子8（MFG-E8）、补体激活经典途径中的亚成分（C1q）、脑源性神经营养因子（BDNF）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的血清水平，我们可以深入了解疾病各个阶段小胶质细胞的激活状态。如果这个假设成立，就可以开发新的靶向药物，以减少皮质灰质的恶化，从而可能改善阴性症状和认知缺陷。
