1.A functional magnetic resonance imaging study on correlation between dynamic amplitude of low frequency fluctuation and spatial navigation impairment in individuals with subjective cognitive decline
Futao CHEN ; Cong LONG ; Qian CHEN ; Yajing ZHU ; Xin ZHANG ; Jiu CHEN ; Jiaming LU ; Bing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):385-392
Objective:To explore the differences in dynamic spontaneous brain activity in individuals with subjective cognitive decline (SCD) and its correlation with spatial navigation ability in SCD subjects.Methods:A total of 72 SCD subjects(SCD group) and 67 normal controls (NC group) matched for age, gender and education level were recruited from September 2020 to February 2023 at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) examinations, spatial navigation tests and cognitive function assessments. The rs-fMRI time series were segmented using a sliding time window method, and statistical analyses were carried out using SPSS 26.0 software to compare the differences in the dynamic amplitude of low frequency fluctuation (dALFF) between the two groups. Correlation analysis was conducted between dALFF values in different brain regions and scale scores and spatial navigation tests.Results:Compared with the NC group, the dALFF variability in the right precuneus(0.119±0.021, 0.130±0.031) and left cuneus(0.143±0.034, 0.156±0.032) in SCD group decreased ( t=-3.41, -3.12, P<0.05, FDR corrected), and the dALFF variability in the right middle occipital gyrus(0.146±0.023, 0.137±0.020) and right angular gyrus(0.148±0.025, 0.139±0.026) increased ( t=4.51, 3.36, both P<0.05, FDR corrected). The temporal variability of dALFF in the right precuneus in SCD group was negatively correlated with egocentric spatial navigation ( r=-0.341, P=0.025), delayed allocentric spatial navigation ( r=-0.286, P=0.035) and memory function ( r=-0.332, P=0.009). The temporal variability of dALFF in the left middle occipital gyrus was positively correlated with language function ( r=0.339, P=0.015) and visuospatial function ( r=0.343, P=0.008) in SCD group. Conclusions:The temporal variability of dALFF in the right precuneus and the left middle occipital gyrus may be the neurobiological basis of cognitive decline and spatial navigation impairment in SCD subjects, and it can be used as a potential imaging marker for early identification of SCD patients.
2.The different prefrontal activation in major depressive disorder and schizophrenia under eye emotion discrimination task: a near-infrared spectroscopy study
Yuan LI ; Huan HUANG ; Rui XU ; Shijing WANG ; Xuan QIN ; Yunlong PENG ; Wei YUAN ; Huiling WANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):393-399
Objective:To compare the differences in prefrontal activation patterns between major depressive disorder and schizophrenia during the eye basic emotion discrimination task (EBEDT).Methods:Using functional near infrared spectroscopy (fNIRS) technology and block design, the changes of prefrontal lobe oxyhemoglobin (Oxy-Hb) concentrations under EBEDT in 40 patients with major depressive disorder, 47 patients with schizophrenia and 55 normal controls were compared. Subsequently, employing years of education as a covariate, an analysis of covariance was performed on the EBEDT behavioral results and the changes in prefrontal Oxy-Hb concentrations in the three groups.The statistical software was SPSS 25.0.Results:(1)The correct number of EBEDT in schizophrenia group (13.93±7.67) was significantly lower than that in major depressive disorder group (19.26±8.07) and normal control group (21.79±6.36)(both P<0.05), and the EBEDT reaction time in schizophrenia group ((3.97±1.77) s) was significantly longer than those in major depressive disorder group ((3.21±1.27) s) and normal control group ((2.63±0.62) s)(both P<0.05).(2)During the EBEDT task block, the normal control group showed increased activation levels in the frontal polar region, Broca's area, anterior motor cortex and supplementary motor area (SMA) compared with the control block( t=2.02-3.18, all P<0.05); and the schizophrenia group showed increased activation levels in the frontal eye field compared with the control block( t=2.26, P=0.03); while the major depressive disorder group exhibited decreased activation levels in the entire prefrontal lobe compared with the control block( t=-3.47--2.34, all P<0.05). (3)During the emotion recognition task of EBEDT, the activation levels of the frontal polar area (ch37), dorsolateral prefrontal cortex (ch31), Broca's area (ch49, ch51, ch53), and SMA (ch1, ch47, ch52) were significantly different among the major depressive disorder, schizophrenia and normal controls( F=3.23-5.53, all P<0.05). Further pairwise comparisons showed that the activation levels in all the above pathways were lower in the major depressive disorder group than those in the normal control group, and the activation levels in Broca's area (ch53) and SMA area (ch52) were lower in the schizophrenia group than those in the normal control group, while the activation levels in the frontal polar area (ch37) and Broca's area (ch49) were lower in the major depressive disorder group than those in the schizophrenia group(all P<0.05). Conclusions:In EBEDT, the activation patterns of the prefrontal cortex are different between patients with major depressive disorder and patients with schizophrenia. Patients with major depressive disorder have a decrease in prefrontal cortex activation, while patients with schizophrenia have an increase in the frontal eye field activation.The activation levels in prefrontal cortex of both patients group are lower than that of normal controls. Meanwhile, the prefrontal cortex activation level of patients with major depressive disorder is lower than that of patients with schizophrenia.
3.Evaluation of brain glymphatic system function in patients with bipolar disorder based on diffusion tensor imaging along the perivascular space
Liqian CUI ; Huixing ZENG ; Yixin CHEN ; Yizhi ZHANG ; Jinbiao LI ; Wenhao DENG ; Liping CAO
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):400-405
Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.
4.The correlation between amplitude of low frequency fluctuation of spontaneous brain activity in resting-state and cognitive fusion in patients with major depressive disorder
Xiao DONG ; Huichang QIAN ; Xiaoman CHENG ; Xiaozheng LIU ; Jiehua MA ; Dandan LIU ; Jian LIU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):406-411
Objective:Based on the pathological model of acceptance and commitment therapy(ACT), to explore the correlation between cognitive fusion and resting-state spontaneous brain activity amplitude of low frequency fluctuation in patients with major depressive disorder(MDD).Methods:Patients with MDD ( n=19) and healthy controls (HCs, n=19)matched with gender, age, and years of education were enrolled from August 2022 to May 2023 in Hangzhou Seventh People's Hospital. 17-item Hamilton depression rating scale(HAMD-17) and cognitive fusion questionnaire(CFQ) were used to estimate the depressive symptoms and cognitive fusion of the participants. The amplitude of low frequency fluctuation(ALFF) data were collected on a 1.5 T-GE scanner. Based on DPABI v7.0 software of MATLAB 7.11.0 (R2018b), two independent sample t-test was used to compare the ALFF of the MDD group and HC group. ALFF values and the cognitive fusion scale scores were investigated by Pearson correlation analysis. Results:Compared with HCs, ALFF in patients with MDD was decreased relatively in the left triangular part of the inferior frontal gyrus(MNI: x, y, z=-36, 24, 21; t=-2.107, P=0.042), the right cuneus(CUN; MNI: x, y, z=12, -87, 24; t=-8.635, P<0.001) as well as the left calcarine fissure and surrounding cortex(MNI: x, y, z=-18, -57, 6; t=-14.188, P<0.001), while increased relatively in left superior occipital gyrus(MNI: x, y, z=-21, -72, 33; t=-7.253, P<0.001). There was a significant negative correlation between cognitive fusion and ALFF values of abnormal activity in left IFGtriang (belonging to ECN)( r=-0.57, P<0.05). Conclusion:There is a correlation between cognitive fusion and resting-state spontaneous brain activity ALFF in patients with MDD. Both cognitive fusion and depressive symptoms may affect patients' cognitive control deficits through multiple sources.
5.Imaging-assisted diagnostic model for schizophrenia using multimodal magnetic resonance imaging
Yanmin PENG ; Meiting BAN ; Ediri Wasana ARACHCHI ; Chongjian LIAO ; Qi LUO ; Meng LIANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):412-418
Objective:To develop an imaging-assisted diagnostic tool for schizophrenia based on multimodal magnetic resonance imaging and artificial intelligence techniques.Methods:Three independent datasets were utilized. For each subject, four brain structural metrics including grey matter volume (GMV), white matter volume (WMV), cortical thickness (CT) and deformation-based morphometry (DBM) indicators were extracted from the structural magnetic resonance imaging (sMRI) data, and three brain functional metrics including amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were extracted from the functional magnetic resonance imaging (fMRI) data. To distinguish patients with schizophrenia and healthy controls, single-metric classification models and multi-metrics-fusion classification models were trained and tested using a within-dataset and a between-dataset cross-validation strategy.Results:The results of within-dataset cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 86.18% (FC), while the multi-metric-fusion classifications could reach an accuracy of 90.21%. The results of between-datasets cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 69.02% (ReHo), while the multi-metric-fusion classifications could reach an accuracy of 71.25%.Conclusion:The functional metrics generally outperforms the structural metrics for the classification between patients with schizophrenia and heathy controls. Additionally, fusion of multi-modal brain imaging metrics can improve the classification performance. Specifically, the fusion of CT, DBM, WMV, FC and ReHo demonstrates the highest classification accuracy, which is a potential tool for imaging-assisted diagnosis of schizophrenia.
6.Characteristics of brain network topological properties in schizophrenic patients based on machine learning
Lunpu AI ; Yangyang LIU ; Ningning DING ; Entu ZHANG ; Yibo GENG ; Qingjiang ZHAO ; Haisan ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):419-424
Objective:To analyze brain topological property data through machine learning methods and explore changes in brain network topological properties in patients with schizophrenia.Methods:From January 2022 to August 2023, functional magnetic resonance imaging data of 60 patients with schizophrenia and 56 healthy controls were collected , and the data were preprocessed to construct brain functional networks and extract global and nodal topological properties. All subjects were divided into a training group and a testing group.The data of training group were fitted based on support vector machine, and the predictive performance was evaluated through cross-validation.The model was optimized by recursive feature elimination algorithm, then the indicators that contributed the most to predictive performance were extrated.The classification performance of the testing group was calculated based on the trained model with optimal predictive performance.SPSS 20.0 software was used for data analysis, the independent t-test and χ2 test were used for comparing the differences between the two groups. Results:The support vector machine achieved an accuracy of 75.00% in predicting the test group of schizophrenia patients based on all indicators. After removing redundant features and combining with the recursive feature elimination algorithm, the accuracy of the SVM model in predicting the test group increased to 90.00%. The nodal global efficiency(Ne)of the left superior temporal gyrus, right dorsal agranular insula, bilateral dorsal granular insula, bilateral caudal cingulate gyrus, and left lateral orbitofrontal cortex in the model contributed the most to classification.Compared to the control group, patients with schizophrenia had abnormal Ne values in these brain regions.Conclusion:There are multiple brain regions with abnormal Ne values in patients with schizophrenia, indicating that the abnormalities in information integration and transmission functions may be related to the imbalance in the dynamic equilibrium of the patients' brain networks.
7.Study of large-scale functional brain networks and topological properties in patients with major depressive disorder
Hao SUN ; Rui YAN ; Lingling HUA ; Zhilu CHEN ; Jiabo SHI ; Yu CHEN ; Xiaoqin WANG ; Qing LU ; Zhijian YAO
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):425-431
Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.
8.Cerebral magnetic resonance diffusion kurtosis imaging in active Crohn's disease patients with or without anxiety
Kecen YUE ; Jingwen SUN ; Xintong WU ; Haifeng SHI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):432-438
Objective:To investigate the changes of brain microstructure in active Crohn's disease (CD) patients with or without anxiety by diffusion kurtosis imaging (DKI), and to explore the relationship between brain microstructure and anxiety in patients with CD.Methods:Thirty-seven patients with CD who were treated in Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2022 to January 2023 were included as the CD group, and 20 healthy subjects were included as the healthy control group during the same period. All subjects were assessed with hospital anxiety and depression scale-anxiety (HADS-A) before magnetic resonance imaging(MRI) scan. According to the HADS-A score, CD patients were divided into the CD group with anxiety (16 cases) and the CD group without anxiety (21 cases). After MRI scan, DKI parameters were obtained by DKE software. One-way analysis of variance was used to compare DKI parameters between the two groups of CD patients and the healthy control group. Pearson correlation was used to analyze the correlation between DKI parameters in different brain areas and psychological scale scores in the two groups of CD patients.Results:The axial diffusion kurtosis(AK)values in the right insula, the left superior temporal gyrus, the right thalamus, the left middle temporal gyrus, the right inferior temporal gyrus, the left lingual gyrus and the right anterior cuneus were significantly different among the three groups ( F=3.060-9.627, all P<0.05).There were significant differences in the radial diffusion kurtosis(RK) values in the right cerebellar region 6 and the left hippocampus among the three groups ( F=4.124, 3.536, 4.200, all P<0.05). Further multiple comparison results showed that the AK values of the right insula (0.701±0.028)( P=0.019), the left superior temporal gyrus (0.764±0.016)( P=0.002) and the right thalamus (0.728±0.016)( P=0.001) in the CD group without anxiety were lower than those of the healthy control group(0.726±0.010, 0.780±0.015, 0.771±0.082), and the RK value of the right cerebellar region 6 ( P=0.021) was lower than that of the healthy control group. The AK values of the right insula ( P=0.023), the left superior temporal gyrus ( P=0.015), the right thalamus ( P=0.031), the left middle temporal gyrus ( P=0.006), the right inferior temporal gyrus ( P=0.001) and the left lingual gyrus ( P=0.007) in the CD group with anxiety were lower than those in the healthy control group. The RK values of right cerebellar region 6 ( P=0.012) and left hippocampus ( P=0.004) were lower than those of healthy control group. The AK values of the right insula ( P=0.002) and the right anterior cuneus ( P=0.017) in the group with anxiety were lower than those in the CD group without anxiety. In the CD group with anxiety, the AK value of the right insula was correlated with erythrocyte sedimentation rate(ESR)( r=-0.47, P=0.048), HADS-A score ( r=-0.68, P=0.002), SES-CD( r=-0.84, P<0.001) and duration of disease ( r=-0.61, P=0.008) were negatively correlated. AK values in the left superior temporal gyrus with anxiety CD group were negatively correlated with HADS-A score ( r=-0.51, P=0.030) and SES-CD score ( r=-0.48, P=0.046). Conclusion:The microstructure of some brain regions was damaged in CD patients with or without anxiety, which was manifested as decreased RK and AK values in DKI parameter values, which may be related to the anxiety state in active CD patients.
9.Effects of docosahexaenoic acid on hippocampal neuronal apoptosis and JNK protein in rats with subarachnoid hemorrhage
Xiaoyuan HUANG ; Tohti MAMATEMIN ; Maoliti WULABIEKE ; Cheng ZHANG ; Yonggang WU ; Jichao WANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):439-444
Objective:To investigate the potential effect and mechanism of docosahexaenoic acid(DHA) on hippocampal neuronal apoptosis and c-Jun N-terminal kinase(JNK) protein in rats with subarachnoid hemorrhage(SAH).Methods:Forty eight SPF-grade male SD rats were randomly divided into control group, sham group, model group and DHA intervention group according to the random number table method, with 12 rats in each group.The rats in model group and DHA group were injected with autologous blood(0.3 mL) into the optic chiasma to establish the SAH model.Rats in model group were intraperitoneally injected with DHA(35 mg/kg) 3 hours after SAH model establishment, rats in sham operation group were injected with 0.3 mL 0.9% sodium chloride solution into the optic chiasma, and rats in control group were fed normally.Neurobehavioral function of all rats was evaluated after 24 hours.The apoptosis of neuron was observed by TUNEL staining, and the expression of phosphorylated JNK(p-JNK)and apoptosis-related proteins Bax and Bcl-2 was observed by Western blot.Statistical analysis was performed using GraphPad Prism 7.0 software.One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1)The differences in neurobehavioral function scores among the 4 groups of rats were statistically significant( F=103.60, P<0.05), the neurobehavioral function scores in model group(8.67±1.37) and DHA intervention group(13.67±1.51) were lower than that in control group(18.00±0.00) and sham group(17.67±0.52)( all P<0.05), while the neurobehavioral function score in DHA intervention group was higher than that in the model group( P<0.05).(2)The results of TUNEL staining showed that there were statistical differences in the number of hippocampal neuron apoptosis among the 4 groups( F=30.76, P<0.05), the number of hippocampal neuron apoptosis in model group(55.67±5.28) was higher than those in control group(25.83±7.06) and sham group(25.50±6.72) (both P<0.05), the number of hippocampal neuron apoptosis in DHA intervention group(35.17±5.78) was lower than that in model group.(3)The results of Western blot showed that there were no statistical differences in the Bax protein levels among the four groups( F=2.00, P>0.05).There were statistical differences in the expression levels of Bcl-2, p-JNK and Bax/Bcl-2 ratio among the 4 groups( F=8.48, 5.69, 5.39, all P<0.05).There was no statistical difference in Bcl-2, p-JNK protein levels and Bax/Bcl-2 ratio between the control group and sham group(all P>0.05).The p-JNK protein levels and Bax/Bcl-2 ratio in model group ((1.93±0.25), (2.05±0.86)) were higher than those in sham group ((1.42±0.33), (1.05±0.26)) (both P<0.05), the Bcl-2 protein level in model group (1.04±0.23) was lower than that in sham group (1.61±0.16) ( P<0.05).The p-JNK protein level and Bax/Bcl-2 ratio in DHA intervention group((1.43±0.33), (1.19±0.30)) were lower than those in model group(both P<0.05), the Bcl-2 protein level in DHA intervention group(1.42±0.28) was higher than that in model group( P<0.05). Conclusion:DHA can reduce neuronal apoptosis, inhibit the activation of p-JNK and improve neurological function of SAH model rats.
10.Neuroprotective effect and mechanism of Ginkgo biloba extract on rotenone-induced damage in PC12 cells
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):445-451
Objective:To investigate the protective effects and mechanisms of Ginkgo biloba extract (EGb) on rotenone-induced damage in PC12 cells, a pheochromocytoma cell line derived from rat adrenal medulla.Methods:PC12 cells were divided into blank control group, rotenone model group (0.5 μmol/L rotenone) and EGb761 group (0.5 μmol/L rotenone+ 100 mg/L EGb761). Mitochondrial membrane potential was detected by JC-1 probe. Mitochondrial energy metabolism levels were measured using a Seahorse XFe24 analyzer. Furthermore, protein expression levels of caspase-3, cleaved-caspase-3, adenosine monophosphate-activated protein kinase(AMPK), phosphorylated-AMPK (p-AMPK), phosphatidylinositol-3-kinase(PI3K), phosphorylated-PI3K(p-PI3K), serine/threonine-protein kinase (AKT), phosphorylated-AKT(p-AKT), mammalian target of rapamycin (mTOR), and phosphorylated-mTOR (p-mTOR) were determined by Western blot.SPSS 20.0 software was used for data analysis.One-way ANOVA was used for multiple group comparisons and LSD test was used for further pairwise comparisons.Results:(1) JC-1 staining showed statistically significant differences in the mitochondrial membrane potential of PC12 cells among the three groups ( F=34.89, P<0.05). EGb761 significantly increased the mitochondrial membrane potential in PC12 cells compared to the rotenone model group (fluorescence intensity ratio: (1.30±0.16), (0.81±0.15), P<0.05). (2) Seahorse experiments showed statistically significant differences in the basal respiration, ATP production, maximal respiration and spare respiratory capacity of PC12 cells among the three groups ( F=38.07, 64.18, 64.42, 34.62, all P<0.05). EGb761 significantly increased the basal respiration ((73.02±13.81)pmol/min, (33.69±3.91)pmol/min), ATP production ((57.08±7.31)pmol/min, (18.08±2.50)pmol/min), maximal respiration ((177.70±17.14)pmol/min, (113.12±13.24)pmol/min), and spare respiratory capacity ((104.72±8.58)pmol/min, (79.43±9.35)pmol/min) of PC12 cells compared to the rotenone model group (all P<0.05). (3) Western blot showed statistically significant differences in the ratio of cleaved-caspase-3/caspase-3、p-AMPK/AMPK、p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR in PC12 cells among the three groups ( F=48.05, 28.68, 33.73, 45.81, 17.39, all P<0.05). EGb761 significantly decreased the ratio of cleaved-caspase-3/caspase-3 ((1.95±0.36), (3.56±0.37)) and p-AMPK/AMPK((1.49±0.19), (2.25±0.27)) and increased the ratio of p-PI3K/PI3K((0.75±0.07), (0.44±0.07)), p-AKT/AKT((0.74±0.06), (0.36±0.09)), and p-mTOR/mTOR((0.90±0.06), (0.62±0.07)) in PC12 cells compared to the rotenone model group (all P<0.05). Conclusion:EGb761 has a protective effect on rotenone-induced PC12 cells, which was associated with the inhibition of AMPK activation and the PI3K/AKT/mTOR pathway, increasing mitochondrial activity and inhibiting apoptosis.

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