1.Neuroremodeling and depression
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(12):1142-1146
Depression is a common mental and psychiatry disorder. Depression is easy to recur and hard to cure.These urgent problems origin from the limited understanding of this disease and the big heteroge-neity in its genology. Generalized from recent relative papers we discovered that the important onset and sus-taining basis of depression is neuroremodeling,which includes the persistent changes of histocytology,ultra-structure of synapse and abnormal expressions of gene and protein of neurons in key brain regions,and so on. These changes affect the correct dealing on the neural message which lead to depression and become the sus-taining biological basis. Therefore the key strategies to prevent and cure depression lie on preventing,individ-ual therapy and reversing neuroremodeling.
2.The effects of acupuncture combined with speech therapy on aphasia caused by stroke: clinical and fMRI study
Jinhuan LIU ; Jun CHEN ; Zihu TAN ; Ni LI ; Yilin ZHAO
Chinese Journal of Physical Medicine and Rehabilitation 2013;35(7):552-556
Objective To observe and compare the effects of acupuncture and acupuncture plus speech therapy on activation of the brain areas in aphasic patients by use of oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI).Methods Twenty patients with aphasia caused by stroke were randomized into two groups by use of random number table (10 cases in each group):an experimental group subject to acupuncture treatment combined with speech therapy,and a control group subject to speech therapy only.All the cases were dextromanuality.On admission and after 1 month of treatment,BOLD-fMRI was used to test signals of the activated brain areas of both group,and Aphasia Battery of the Chinese (ABC) was employed to evaluate the changes of speech ability of the patients.Results During the study,1 case from control group was unable to do the post-intervention evaluation due to onset of the second stroke.The effective rates of the control and experimental group were 55.56% and 100.00%,respectively,and recovery of verbal ability in experimental group was significantly better than in control group (P < 0.05).The active volume and extent in brain were significantly increased in both groups (P <0.05),and a comparison between the two groups showed that the changes in activation volume and extent of the brain were significantly greater extensive in experimental group than in the control group,especially in bilateral frontal lobe,cuneus,posterior cingulate gyrus,lingual gyrus,occipital lobe,splenium of corpus callosum,cerebellar hemisphere,and the left precentral gyrus,post-central gyrus,paracentral lobule,temporal lobes,angular gyrus,precuneus,and the right hippocampus,parahippocampus gyrus.Conclusion Acupuncture combined with speech therapy could cause changes in activation patterns of the brain areas,which may contribute to the improvement of verbal ability of the aphasic patients.
3.Modified Shuyuwan Ameliorates Depressive Behaviors and Promotes Myelin Regeneration in Mouse Model of Vascular Dementia Complicated with Depression by Regulating Energy Metabolism of Myelin Axons via MCT1
Wenjing YAN ; Zihu TAN ; Qiong YANG ; Qingwei XIANG ; Jianjie ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):21-29
ObjectiveTo explore the mechanism of modified Shuyuwan in treating vascular dementia (VaD) complicated with depression in mice. MethodThe VaD model was established by bilateral carotid artery stenosis (BCAS) in seven 3-month-old male C57/BL6 mice. The regional cerebral blood flow (rCBF) of mice was measured by laser speckle imaging before and after BCAS surgery. Then, the BCAS method was combined with chronic unpredictable mild stress (CUMS) to establish a mouse model of VaD complicated with depression. BCAS/CUMS mice were assigned into BCAS/CUMS, fluoxetine (0.01 g·kg-1), and high-, medium-, and low-dose (20, 10, 5 g·kg-1, respectively) modified Shuyuwan groups. The shame group underwent sham operation without CUMS (n=10). The tail suspension test and sucrose preference test were carried out to examine the depressive behaviors of mice. The distribution and expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neurofilament heavy polypeptide (NF200), and anti-non-phosphorylated neurofilament epitope antibody (SMI32) in the corpus callosum (CC) were detected by the immunofluorescence assay. Western blot was employed to determine the protein levels of monocarboxylate transporter 1 (MCT1), MBP, MAG, oligodendrocyte glycoprotein (MOG), amyloid precursor protein (APP), NF200, contactin-associated protein (Caspr), and voltage-gated sodium channel (Nav1.6) in the corpus callosum. The level of lactic acid in the serum was measured by the lactic acid assay kit, and the ultrastructure of myelin was observed by ultraprojective electron microscope. ResultLaser speckle imaging showed that rCBF decreased immediately 10 min after BCAS surgery (P<0.01), and the rCBF was still cerebral hypoperfusion and did not return to the preoperative level 2 weeks after surgery. Behavioral test results showed that compared with the sham group, the BCAS/CUMS group presented decreased percentage of sucrose preference (P<0.01) and prolonged immobile time in the tail suspension test (P<0.01). Compared with the BCAS/CUMS group, fluoxetine and modified Shuyuwan increased the percentage of sucrose preference (P<0.01) and shortened the immobile time in the tail suspension test (P<0.01). The level of lactic acid was the highest in the BCAS/CUMS mice (P<0.01), and modified Shuyuwan lowered the lactic acid level (P<0.01). Immunofluorescence results showed that compared with the sham group, the BCAS/CUMS group presented decreased fluorescence intensity of MAG, MBP and NF200 and increased fluorescence intensity of SMI32 in the corpus callosum, and such changes were reversed by modified Shuyuwan at different doses and fluoxetine. Western blot results showed that compared with the sham group, the BCAS/CUMS modeling down-regulated the protein levels of MCT1, MBP, MOG, MAG, NF20, and Caspr (P<0.05, P<0.01) and up-regulated the protein levels of APP and Nav1.6 in the corpus callosum, and the above trends were reversed by modified Shuyuwan (P<0.05, P<0.01). Compared with the sham group, BCAS/CUMS modeling led to myelin ultrastructure damage and axon atrophy, which were alleviated by modified Shuyuwan. ConclusionModified Shuyuwan can ameliorate the transport disorder of lactic acid between myelin sheath and axon by upregulating the expressin of MCT1, promote the regeneration of myelin sheath in the corpus callosum, and improve the integrity of myelin sheath structure, thereby alleviating depression in VaD mice.
4.Effect of Modified Shuyuwan on Hippocampal Myelin Sheath Injury in Vascular Dementia Rats Through Cx43/Glu/AMPAR Pathway
Jianting WANG ; Zihu TAN ; Jianjie ZHOU ; Jing WANG ; Qiong YANG ; Yu LIU ; Xianwei LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):38-46
ObjectiveTo investigate the effect and mechanism of modified Shuyuwan (SYW) on hippocampal myelin sheath injury in vascular dementia (VD) model rats. MethodSixty male SD rats of SPF grade were randomly divided into sham operation group, model group, and high-, medium- and low-dose modified SYW groups, with 12 rats in each group. The VD model was induced by bilateral carotid artery ligation in rats of the groups except for those of the sham operation group. After modeling, rats were screened by the water maze test, followed by drug treatment by gavage. Specifically, rats in the modified SYW groups were treated with modified SYW at 10, 5, 2.5 g·kg-1·d-1, accordingly, and those in other groups were administered with the same amount of normal saline. After intragastric administration for 28 days, the spatial learning and memory abilities of rats were detected by the water maze test. The hippocampal neuron structure was observed by hematoxylin-eosin (HE) staining. The content of hippocampal tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and glutamate (Glu) was observed by biochemical detection. The hippocampal expression of myelin basic protein (MBP), astrocyte activation marker glial fibrillary acidic protein (GFAP), and connexin 43 (Cx43) was detected by immunofluorescence detection. The myelin sheath structure in the hippocampus was observed by the electron microscope. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) and Cx43 protein expression was detected by Western blot. ResultCompared with the sham operation group, the model group showed prolonged escape latency (P<0.01), decreased times of crossing the original platform and percentage of target quadrant detention time (P<0.01), disordered neuron structure in the hippocampal CA1 region, loose myelin sheath lamella with blurry edge, up-regulated expression levels of TNF-α, IL-6, and Glu in the hippocampal CA1 region, especially Glu (P<0.01), reduced expression of AMPAR (P<0.01), increased protein expression of p-AMPAR and Cx43 (P<0.01), significantly dwindled protein expression of MBP in the myelin sheath, and enhanced fluorescence co-labeled by GFAP and Cx43. Compared with the model group, the modified SYW groups showed shortened escape latency (P<0.05), increased times of crossing the original platform and percentage of target quadrant detention time (P<0.05), closely arranged hippocampal neuron structure, denser myelin sheath lamella with clear edge, down-regulated expression levels of TNF-α, IL-6, and Glu in the hippocampal CA1 region, especially Glu (P<0.01), up-regulated AMPAR (P<0.01), reduced protein expression of p-AMPAR and Cx43, especially in the high-dose group (P<0.01), significantly elevated protein expression of MBP in the myelin sheath, and weakened fluorescence co-labeled by GFAP and Cx43, especially in the high-dose group. ConclusionModified SYW can improve the learning and memory abilities of VD rats, and the mechanism may be related to the inhibition of Cx43 expression, reduction of the release of Glu, inhibition of AMPAR-mediated inflammatory response to reduce the production of astrocyte marker GFAP, and promotion of the expression of MBP protein to alleviate myelin injury.