ABSTRACT
The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.
Subject(s)
Animals , Mice , Cell Differentiation , Physiology , Demyelinating Diseases , Lysophosphatidylcholines , Toxicity , Mice, Inbred C57BL , Nerve Tissue Proteins , Metabolism , Oligodendrocyte Precursor Cells , Cell Biology , Metabolism , Oligodendroglia , Cell Biology , Metabolism , Remyelination , Physiology , Transcription Factors , MetabolismABSTRACT
Objective To explore the normal values for two-dimension solid state high resolution anorectal manometry (HRAM) in healthy adult volunteers.Methods The healthy adult volunteers were recruited by advertisement and underwent solid state HRAM in the left lateral position.Anorectal pressures and rectal sensation were recorded and analyzed.Results (1) A total of 126 Chinese healthy adult volunteers (male:50 cases (39.7％);age:(37.5 ± 14.2) years old) were recruited in this study.(2)Mean anal resting pressure (MERP) was (71.8 ± 17.3) mmHg (1 mmHg =0.133 kPa).Maximum anal resting pressure (MARP) was (79.3 ± 17.8) mmHg,Maximum anal squeeze pressure (MSP) was (178.7 ± 52.8) mmHg.Anal high pressure zone (HPZ) length was (3.4 ± 0.6) cm.During simulated evacuation,residual anal pressure (RAP) was (63.8 ±20.5) mmHg,and anal relaxation rate (ARR) was (37.0 ± 11.5) ％.Rectal threshold volume for first sensation (FST),desire to defecate (DDT),urgency to defecate (UDT) and maximum discomfort (MDT) was (47.4 ±10.0) ml,(84.5 ±18.2) ml,(125.8 ± 28.5) ml,and (175.5 ±36.1) ml,respectively.(3) Compared with female subjects,male subjects had higher MSP [(211.0 ± 50.7) mmHg vs (157.5 ± 42.5) mmHg],RAP [(71.6 ± 18.1) mmHg vs (58.8 ± 20.5) mmHg]and rectal MDT[(187.0 ±36.4) mmHg vs (168.0 ±34.1)mmHg],but lower ARR [(32.1 ±8.0)％ vs (40.2 ±12.3)％],all P＜0.01.(4) MERP,MARP,MSP and rectal MDT were higher in young group (≤ 40 years old),all P ＜ 0.05.Conclusions These observations provide normal values for two-dimension solid state HRAM,which have significant difference between genders and different age groups.
ABSTRACT
Objective To evaluate the feasibility of liver senescence model with senescence accelerated mouse prone 8 (SAMP8), and to explore the possible mechanism of oxidative stress in the process of liver aging in SAMP8. Methods Male SAMP8 mice at the age of 9 months were chosen as research objects, and senescence accelerated mouse resistance 1 (SAMR1) mice were used for normal control. Histopathological changes in the liver of SAMR1 and SAMP8 mice were observed by hematoxylin-eosin (HE), Sudan Ⅳ and Masson staining. Senescence associated β-galactosidase activity was measured by histoehemical staining method, and the activities of superoxide dismutase (SOD), eatalase (CAT), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in liver homogenate were examined by chemical colorimetry. Results Compared with SAMR1 group, the liver degenerative changes of SAMP8 mice were observed by microscopy, such as extensive fatty degeneration, focal necrosis of hepatocytes and inflammatory cells infiltration. Meanwhile, senescence associated β-galactosidase-positive cells were significantly increased in SAMP8 group [(78.1±11.0) vs.( 23.9±8.8),t=10.887, P<0.01]. In addition, the activities of SOD, CAT and GSH-Px in liver homogenate were decreased [SOD: (214.8 ± 34.8) vs. ( 295.3 ± 29.7), t = 4.975,P<0.01;CAT: (23.0±4.0) vs. ( 36.3±8.3),t=4.084,P<0.01;GSH-Px: (524.0±74.2) vs. (648. 4±102.8) ,t=2. 776, P<0. 05]and the level of MDA was markedly increased ((2.3±0.2) vs. (1.8±0. 1),t = 6. 329, P<0. 01]. Conclusions SAMP8 mice is a feasible animal model for the study of liver senescence, and oxidative stress may play an important role in the process of liver aging in SAMP8.