Nobuki Kuwano1, Takahiro A Kato2, Masato Mitsuhashi3, Mina Sato-Kasai1, Norihiro Shimokawa1, Kohei Hayakawa1, Masahiro Ohgidani1, Noriaki Sagata1, Hiroaki Kubo1, Takeshi Sakurai4, Shigenobu Kanba1. 1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. 2. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: takahiro@npsych.med.kyushu-u.ac.jp. 3. NanoSomiX, Inc., Irvine, CA, USA. 4. Faculty of Medicine/International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan.
Abstract
BACKGROUND: Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. METHODS: As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. RESULTS: Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. LIMITATIONS: We did not actually extract NDE from peripheral blood. CONCLUSIONS: Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.
BACKGROUND:Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, humanNDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. METHODS: As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDDpatients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. RESULTS: Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. LIMITATIONS: We did not actually extract NDE from peripheral blood. CONCLUSIONS: Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.
Authors: Mansour A Alghamdi; Hilary J Wallace; Phillip E Melton; Eric K Moses; Andrew Stevenson; Laith N Al-Eitan; Suzanne Rea; Janine M Duke; Patricia L Danielsen; Cecilia M Prêle; Fiona M Wood; Mark W Fear Journal: Biomedicines Date: 2020-06-28
Authors: Gayatri Gopal Shetgaonkar; Shirleen Miriam Marques; Cleona E M DCruz; R J A Vibhavari; Lalit Kumar; Rupesh Kalidas Shirodkar Journal: Drug Deliv Transl Res Date: 2021-08-07 Impact factor: 4.617