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The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.
Subject(s)
Transcranial Direct Current Stimulation/methods , Motor Cortex/physiology , Neurons , Transcranial Magnetic StimulationABSTRACT
Objective: Sauna bathing is a popular recreational activity and has long since been used to relieve stiff necks and low back pain. Recently, low-temperature sauna has been used to treat congestive heart failure (CHF), coronary artery diseases, chronic fatigue syndrome, and chronic pain. During 1960-1970, thermal stimulation was applied to the patients with renal failure. We could not find the subsequent reports, and the long-term effects are unclear. The purpose of this experiment was to verify the safety of systemic low-temperature sauna treatment (ST) for the 5/6 remnant kidney mouse and to examine the effect of ST on urinary protein excretion. Materials and Methods: The C57BL/6 mice were divided into the following 4 groups; group 1: sham-operated and non-sauna treatment mice (sham+non-ST group: n = 5), group 2: sham-operated and ST mice (sham+ST group: n = 5), group 3: Nx and non-ST mice (Nx+non-ST group: n = 5), and group 4: Nx and ST mice (Nx+ST group: n = 5). Mice received ST at 41°Cfor 15 min and at 32°Cfor 20 min for 12 weeks using a natural convection dry sauna system. Results: After 12 weeks of ST, no differences were observed in creatinine clearance, body weight, fluid intake, urine volume, serum sodium and potassium levels between ST and non-ST groups. Our results showed a significant increase in eNOS mRNA expression in the Nx+ST group compared to that in the Nx+non-ST group. These results suggest the possibility that mild sauna treatment induces thermal vasodilation effects on glomerulus. Systolic blood pressure and urine protein levels in the Nx groups did not change throughout the intervention. Conclusion: There are no clear adverse events associated with low-temperature sauna. Therefore, this study setting is safe in the CKD model mouse. Renal eNOS mRNA expression was increased by the low-temperature sauna. The present results suggest the possibility that ST might provide a renal protective effect by suppressing glomerular hypertension via stimulation of renal NO production in the CKD model mouse.
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Objective To knockout the murine Txnip gene using microinjection of transcription activator-like effector nuclease ( TALEN) mRNAs.Methods TALEN knockout site recognizing Txnip was designed by tools on line, then constructed the vectors and assayed its cleavage activity at cellular level.TALEN mRNA was transcribed in vitro and microinjected into C57BL/6J mouse zygotes.F0 mice were verified at DNA level with BamHI and TXNIP-knockout mice were obtained.Results We designed and constructed TALENs which recognized and cut the first exon of Txnip, and got four TXNIP knockout mice, among which two were frameshift mutation, demonstrating that the TXNIP-knockout mice were generated by TALEN technique.Conclusions Microinjection of in vitro transcribed TALEN mRNAs into murine zygotes is a highly effective and convenient way to develop TXNIP-knockout mouse model.
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<b>Objective</b>: Sauna bathing is a popular recreational activity and has long since been used to relieve stiff necks and low back pain. Recently, low-temperature sauna has been used to treat congestive heart failure (CHF), coronary artery diseases, chronic fatigue syndrome, and chronic pain. During 1960-1970, thermal stimulation was applied to the patients with renal failure. We could not find the subsequent reports, and the long-term effects are unclear. The purpose of this experiment was to verify the safety of systemic low-temperature sauna treatment (ST) for the 5/6 remnant kidney mouse and to examine the effect of ST on urinary protein excretion. <BR><b>Materials and Methods</b>: The C57BL/6 mice were divided into the following 4 groups; group 1: sham-operated and non-sauna treatment mice (sham+non-ST group: n = 5), group 2: sham-operated and ST mice (sham+ST group: n = 5), group 3: Nx and non-ST mice (Nx+non-ST group: n = 5), and group 4: Nx and ST mice (Nx+ST group: n = 5). Mice received ST at 41°Cfor 15 min and at 32°Cfor 20 min for 12 weeks using a natural convection dry sauna system.<BR><b>Results</b>: After 12 weeks of ST, no differences were observed in creatinine clearance, body weight, fluid intake, urine volume, serum sodium and potassium levels between ST and non-ST groups. Our results showed a significant increase in eNOS mRNA expression in the Nx+ST group compared to that in the Nx+non-ST group. These results suggest the possibility that mild sauna treatment induces thermal vasodilation effects on glomerulus. Systolic blood pressure and urine protein levels in the Nx groups did not change throughout the intervention.<BR><b>Conclusion</b>: There are no clear adverse events associated with low-temperature sauna. Therefore, this study setting is safe in the CKD model mouse. Renal eNOS mRNA expression was increased by the low-temperature sauna. The present results suggest the possibility that ST might provide a renal protective effect by suppressing glomerular hypertension via stimulation of renal NO production in the CKD model mouse.
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Systemic sclerosis (SSc) is characterized by tissue fibrosis and autoimmunity. Although the pathogenic relationship between autoimmunity and clinical manifestations of SSc remains unknown, SSc patients display abnormal immune responses including the production of disease-specific autoantibodies. Previous studies have demonstrated that B cells play a critical role in systemic autoimmunity and disease expression through various functions such as induction of the activation of other immune cells in addition to autoantibody production. CD19 is a crucial regulator of B cell activation. Recent studies demonstrated that B cells from SSc patients showed an up-regulated CD19 signaling pathway that induced SSc-specific autoantibody production in SSc mouse models. CD19 transgenic mice lost tolerance for autoantigen and generated autoantibodies spontaneously. B cells from SSc patients exhibited an overexpression of CD19 that induced SSc-specific autoantibody production in transgenic mice. Moreover, SSc patients displayed intrinsic B cell abnormalities characterized by chronic hyper-reactivity of memory B cells, which was possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a genetic model of SSc, showed augmented CD19 signaling. In bleomycin-induced SSc mouse models, endogenous ligands for toll-like receptor 4 induced by bleomycin stimulated B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, the loss of CD19 resulted in the inhibition of B cell hyper-reactivity and autoantibody production, which are associated with improvements in fibrosis and a parallel decrease in fibrogenic cytokine production by B cells. Taken together, the findings suggest that altered B cell function may result in tissue fibrosis as well as autoimmunity in SSc.
Subject(s)
Animals , Humans , Mice , Autoantibodies , Autoimmunity , B-Lymphocytes , Bleomycin , Cytokines , Fibrosis , Ligands , Lymphocyte Activation , Memory , Mice, Transgenic , Models, Genetic , Scleroderma, Systemic , Toll-Like Receptor 4ABSTRACT
BACKGROUND:It is important to establish an ideal mouse model of severe aplastic anemia for investigating the mechanism and finding new therapies for aplastic anemia. OBJECTIVE:To establish a severe aplastic anemia mouse model by using recombinant human interferon-γand busulfan. METHODS:Sixty healthy Kunming female mice were randomly divided into two groups:model group (n=50) and control group (n=10). The model group was given recombinant human interferon-γat a dose of 1×104 U/d by intraperitoneal injection and busulfan at a dose of 18 mg/(kg·d) through stomach feeding for 7 days. The same volume of physiological saline was given to control group. Multi-parameters, including general condition, body weight, blood cellcount, morphology and biopsy of bone marrow were analyzed in two groups. RESULTS AND CONCLUSION:At day 7 after treatment, the weight, white blood cellcount, hemoglobin, blood platelet, reticulocyte count in model group were significantly lower than control group (P<0.05). Bone marrow smears and biopsy of model group showed marked reduction of bone marrow proliferation and increases of percentages of non-hematopoietic cellclusters and adipose tissue. The oil drop and fat vacuole were apparently seen in the model group. Severe aplastic anemia mouse model can be established by using recombinant human interferon-γand busulfan successful y, which is economic, stable and easy to operate.
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Objective To observe the effect of a Uyghur medicine Munziq Balgam on the mouse model of psoriasis.Methods 130 healthy Kunming mice were used in this study .The mouse model of psoriasis was established by applying 5% propranol hydrochloride emulsion to the mouse ear .The tail and ear skin histology was examined using HE staining, and the serum levels of IL-10, IL-17, IL-23 were measured with ELISA.Results The mice of Munziq Balgam treated groups (2, 4, 8 g/kg) did not show obvious abnormalities of general condition and body weight changes (P >0.05).The 8 g/kg Munziq Balgam treated group showed decreased thymus index (P 0.05). The 2, 4, and 8 g/kg Munziq Balgam treated groups showed promoted formation of epidermis granular layer in the mouse tail skin and improved histology of the ear skin .Conclusions The Uygur medicine Munziq Balgam shows therapeutic effect on experimental mouse models of psoriasis .
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Objective To observe the difference of FKBP-12 expression level between in Alzheimer's disease model mice's brains and in control mice's brains.Methods Taking the Senescence Accelerated Mouse imported from Japan(SAM-P/8)as the Alzheimer's disease model mouse,and SAM-R/1 mouse as control,observe the distribution difference of FKBP-12 between in Alzheimer's disease model mice's brains and in control mice's brains both in mRNA level and in protein level with the methods of RT-PCR and immunohistochemistry staining.The mice were divided into four groups of 4,6,8,10 months old.Results There was no distribution difference of FKBP-12 between in Alzheimer's disease model mice's brains and in control mice's brains both in mRNA level and in protein level.Conclusion FKBP-12 probably has no relativity with the accelerated aging process of the Alzheimer's disease model mice imported from Japan.