Zuogui Jiangtang Jieyu Formula Ameliorates Hippocampal Synaptic Microenvironment Damage in Diabetes with Depression via CD300f/GLUT1 Signaling-Mediated Regulation of Microglial Glucose Metabolism
LIU Jian
LIN Xiaoyuan
LONG Hongping
WANG Yuhong
YANG Hui
Abstract：Objective To explore the protective mechanism of Zuogui Jiangtang Jieyu formula(ZGJTYF)in mitigating hippocampal synaptic microenvironment damage in diabetes with depression(DD)by regulating the CD300f/GLUT1 signaling pathway through microglial glucose metabolism.Methods Primary microglia and hippocampal neurons were isolated,cultured,purified,and identified.An in vitro cell model simulating hippocampal synaptic microenvironment damage under DD-like conditions was established.Experimental groups included:control,model,CD300f blocker CLM-1,ZGJTYF-containing serum,and ZGJTYF-containing serum+CLM-1.Cell imaging was used to observe morphological changes in microglia and hippocampal neurons.Biochemical assays were employed to measure insulin,glucose,lactate levels,and ADP/ATP ratio.MitoSOX fluorescent probe was applied to detect mitochondrial reactive oxygen species(ROS)in hippocampal neurons.TUNEL staining was used to assess neuronal apoptosis.Nissl staining was performed to evaluate synaptic damage.ELISA was utilized to measure 5-HT and dopamine(DA)levels.Immunofluorescence was applied to detect CD300f and GLUT1 expression in microglia,and RIMS3 and PSD95 expression in hippocampal neurons.Western blot was used to quantify RIMS3 and PSD95 protein expression.Results ZGJTYF significantly ameliorated morphological damage in microglia and hippocampal neurons,reduced mitochondrial ROS and apoptosis in hippocampal neurons(P<0.05),and increased monoamine neurotransmitters 5-HT and DA(P<0.05),thereby alleviating synaptic damage.Mechanistic studies revealed that ZGJTYF upregulated CD300f and GLUT1(P<0.05)expression in microglia and increased synaptic proteins RIMS3 and PSD95 in hippocampal neurons(P<0.01),ultimately improving the hippocampal synaptic microenvironment.Conclusion ZGJTYF exhibits a significant protective effect against hippocampal synaptic microenvironment damage in DD,which is associated with the regulation of CD300f/GLUT1 signaling-mediated glucose metabolism in microglia.
Keywords：Zuogui Jiangtang Jieyu formulaDiabetes with depressionMicrogliaCD300fGlucose metabolismHippocampal synaptic microenvironment
Publication Date：2025-10-28
Online Publishing Date：2025-10-29(First online date of this platform, not the publication date of the document)
Pages：8( 1752-1759 )