CXCL8 delivered by plasma-derived exosomes induces the symptoms of post-traumatic stress disorder through facilitating astrocyte-neuron communication. (May 2023)

• Record Type: Journal Article
• Authors: Guo, Juncheng; Chen, Siran; Li, Feiyan; Hou, Shiyi; Guo, Min; Yuan, Xiuhong
• Is Part Of: Journal of psychiatric research. Volume 161(2023)
• Page Start: 261
• Page End: 272
• Publication Date: 2023-05
• Subjects: Post-traumatic stress disorder -- Astrocyte-neuron communication -- Extracellular vesicles -- Astrocytes -- CD63 -- CXCL8; Psychiatry -- Periodicals; Mental Disorders -- Periodicals; Maladies mentales -- Périodiques; Psychiatry; Electronic journals; Periodicals; 616.89005
• DOI: 10.1016/j.jpsychires.2023.02.040
• Languages: English
• ISSNs: 0022-3956

Abstract

Abstract: Extracellular vesicles (EVs) play an important role in post-traumatic stress disorder (PTSD). This study is aimed to investigate the possible molecular mechanism of CD63 mediating CXCL8 delivery via EVs to affect astrocyte-neuron communication in PTSD. The neuron-derived EVs (NDEVs) and astrocyte-derived EVs (ADEVs) were isolated from plasma in PTSD patients. Next, the uptake of EVs by neurons was assessed. Following determination of the interaction between CD63 and CXCL8, gain- and loss-of-function experiments were performed in astrocytes. Finally, a PTSD mouse model was established using the single prolonged stress and electric foot shock to confirm the effects of plasma-derived EVs delivering CXCL8 on anxiety- and depression-like behaviors in PTSD mice. EVs derived from plasma of PTSD patients aggravated anxiety- and depression-like behaviors in PTSD mice. CXCL8 was a key gene upregulated in both NDEVs and ADEVs from plasma of PTSD patients, which could be delivered into EVs by CD63. Meanwhile, CXCL8 was also highly expressed in plasma-derived EVs. In vivo experiments also verified that plasma-derived EVs could enhance astrocyte-neuron communication by delivering CXCL8, and silencing of CXCL8 ameliorated anxiety- and depression-like behaviors in PTSD mice. Taken together, CD63 promotes delivery of CXCL8 via EVs to induce PTSD by enhancing astrocyte-neuron communication, suggesting the potential of CD63 mediating delivery of CXCL8 via EVs as a therapeutic target for PTSD.