Doctoral defence: Ling Yan "Stress-associated immune mechanisms of schizophrenia: the importance of region-specific microglia-neurovascular interaction"

On December 15th Ling Yan will defend a thesis "Stress-associated immune mechanisms of schizophrenia: the importance of region-specific microglia-neurovascular interaction".

Supervisors:
Professor Li Tian, University of Tartu
Professor Cao Song, Guangdong Ocean University (China)
Professor Eero Vasar, University of Tartu

Opponent:
Senior researcher Urtė Neniškytė, Vilnius University

Summary:
Psychiatric disorders are a major source of disability and death for the working-age population and cause considerable economic and healthcare burdens globally. Psychiatric disorders can be caused by miscellaneous intrinsic and extrinsic factors that jointly impact on the brain and behavior. Psychosocial stress is a well-recognized risk factor for onset and development of schizophrenia. Among underlying biological mechanisms, chronic stress disrupts brain blood circulation and exacerbates neuroinflammation. Vascular-associated microglia and monocytes-derived macrophages are the most important regulators for neuroinflammation. To better understand functions of microglia/monocytes in psychiatric disorders through the lens of chronic stress, we performed a series of clinical and preclinical investigations on a cohort of first episode schizophrenia (FES) patients as well as mice undergoing chronic unpredictable stress and olfactory bulbectomy (OBX)-induced stress. In clinical research, we found FES patients suffered with heightened stress, cerebral cortical atrophy, as well as reduced blood nonclassical monocytic abundancy and microglial receptor CSF1R level. In animal models, we found an inhibitor of CSF1R induced anxiety and disrupted vascular association of microglia/macrophages. Besides, we found the olfactory bulb displayed abundant blood vessel-associated microglia/macrophages and was enriched with genes for fatty acid metabolism and angiogenesis. Furthermore, OBX-induced stress responses were rescued in fat-1 mice that produced endogenous n-3 PUFAs. These findings suggest that microglia modulators may benefit stress coping via regulating cerebral blood vasculature in schizophrenia. Our studies hence provide novel knowledge on microglial/monocytic subpopulations and their candidate molecules that may be useful for developing better diagnosis and treatment to tackle psychiatric disorders.

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