title: Cortical gray matter loss in schizophrenia: Could microglia be the culprit?
abstract: 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.
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia. Electronic address: valentino.racki@gmail.com.
authors.forename: Valentino
authors.initials: V
authors.lastname: Rački
authors.affiliation: Clinic of Psychiatry, University Hospital Clinic Rijeka, Croatia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Petrić
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kučić
authors.affiliation: Department of Biotechnology, University of Rijeka, Croatia.
authors.forename: Nika
authors.initials: N
authors.lastname: Gržeta
authors.affiliation: Department of Biotechnology, University of Rijeka, Croatia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Jurdana
authors.affiliation: Clinic of Psychiatry, University Hospital Clinic Rijeka, Croatia.
authors.forename: Ika
authors.initials: I
authors.lastname: Rončević-Gržeta
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000954:Antigens, Surface / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D003024:Clozapine / Q000737:chemistry; D003072:Cognition Disorders; D015922:Complement C1q / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000737:chemistry; D066128:Gray Matter / Q000503:physiopathology*; D006801:Humans; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D017628:Microglia / Q000378:metabolism*; D008894:Milk Proteins / Q000097:blood; D008962:Models, Theoretical; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis; D012559:Schizophrenia / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface; D019208:Brain-Derived Neurotrophic Factor; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C098942:MFGE8 protein, human; D008894:Milk Proteins; D016753:Interleukin-10; D016291:Dizocilpine Maleate; C579455:BDNF protein, human; D015922:Complement C1q; D003024:Clozapine