Oligodendroglial lineage cells go through a series of morphological changes prior to myelination.Sufficient cell process outgrowth and mem brane expansion are required to meet the needs of axon-wrapping and myelin seg...Oligodendroglial lineage cells go through a series of morphological changes prior to myelination.Sufficient cell process outgrowth and mem brane expansion are required to meet the needs of axon-wrapping and myelin segment formation,but which are hard to achieve maldevelopment and remyelination.Quetiapine,an atypical antipsychotic drug,has been proved to promote oligodendrocyte(OL)differentiation and(re)myelination,pending detailed effects and regulatory mechanism.In present study,we showed that quetiapine promoted OL differentiation and myelin segment formation in a short period of treatment,enhanced OL processes outgrowth and membrane expansion,and provided detail evidence that quetiapine relocated nuclear transcription factor Olig1 to cytosol,in which highly correlating with OL morphological transformation.To uncover the underlying mechanism,informatics analyses,including docking and MD studies,were executed.GPR17 was one of the most likely candidates.GPR17 is restricted to oligodendroglial lineage cells in an up-and-down expression pattern and acts as a developmental control timer.展开更多
Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GP...Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders.However,no study has investigated the role of GPR17 in psychiatric disorders.In a well-established chronic restraint stress(CRS)mouse model,using a combination of pharmacological and molecular biology techniques,viral tracing,in vitro electrophysiology recordings,in vivo fiber photom-etry,chemogenetic manipulations and behavioral tests,we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala(BLA)glutamatergic neurons.Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutama-tergic neurons effectively improved anxiety-like behaviors.Overexpression of GPR17 in BLA glutama-tergic neurons increased the susceptibility to anxiety-like behaviors.What's more,BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CAl glutamatergic projection.Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.展开更多
文摘Oligodendroglial lineage cells go through a series of morphological changes prior to myelination.Sufficient cell process outgrowth and mem brane expansion are required to meet the needs of axon-wrapping and myelin segment formation,but which are hard to achieve maldevelopment and remyelination.Quetiapine,an atypical antipsychotic drug,has been proved to promote oligodendrocyte(OL)differentiation and(re)myelination,pending detailed effects and regulatory mechanism.In present study,we showed that quetiapine promoted OL differentiation and myelin segment formation in a short period of treatment,enhanced OL processes outgrowth and membrane expansion,and provided detail evidence that quetiapine relocated nuclear transcription factor Olig1 to cytosol,in which highly correlating with OL morphological transformation.To uncover the underlying mechanism,informatics analyses,including docking and MD studies,were executed.GPR17 was one of the most likely candidates.GPR17 is restricted to oligodendroglial lineage cells in an up-and-down expression pattern and acts as a developmental control timer.
基金National Natural Science Foundation of China(82373860 and 82071202 to Susu Tang,82173805 to Hao Hong)National Innovation and Entrepreneurship Training Program for Undergraduate(202410316198,China).
文摘Anxiety disorders are one of the most epidemic and chronic psychiatric disorders.An incom-plete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders.GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders.However,no study has investigated the role of GPR17 in psychiatric disorders.In a well-established chronic restraint stress(CRS)mouse model,using a combination of pharmacological and molecular biology techniques,viral tracing,in vitro electrophysiology recordings,in vivo fiber photom-etry,chemogenetic manipulations and behavioral tests,we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala(BLA)glutamatergic neurons.Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutama-tergic neurons effectively improved anxiety-like behaviors.Overexpression of GPR17 in BLA glutama-tergic neurons increased the susceptibility to anxiety-like behaviors.What's more,BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CAl glutamatergic projection.Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.
