abdominal-massage-to-improve-motor-dysfunction-rats-with-cerebral

Abdominal Massage to Improve Motor Dysfunction in Rats with Cerebral Palsy

Cerebral palsy (CP) is a disease with a high disability rate and morbidity. The clinical symptoms of cerebral palsy are motor dysfunction and abnormal ...

Fudan University

Cerebral palsy (CP) is a neurodevelopmental disorder usually occurring early in life and persisting through the whole life. Several risk factors, including perinatal hypoxia-ischemia (HI), may contribute to occurrence of CP in preterm infants. DNA hydroxymethylation has been shown to play an important role in neurodevelopment and neurodegenerative disorders. However, the effect of DNA hydroxymethylation in CP remains unknown. The aim of this study is to explore whether and how DNA hydroxymethylation is involved in CP pathogenesis. We observed that overall 5-hydroxymethylcytosine (5hmC) abundance in the cortex of the temporal lobe of rat pups was decreased significantly after hypoxic-ischemic injury, and the reduced expression of Tet1 and Tet2 enzymes might be responsible for this change. Identified differential hydroxymethylation regions (DhMRs) were richly involved in multiple signaling pathways related to neuronal development and function. Furthermore, we found that reduced 5hmC modification on the DhMRs-related genes were accompanied by decrease of their mRNA expression levels. These results suggest that 5hmC modifications are involved in the CP pathogenesis and may potentially serve as a new therapeutic target.

Genome-Wide Alteration of 5-Hydroxymethylcytosine in Hypoxic-Ischemic Neonatal Rat Model of Cerebral Palsy.

In addition to abnormalities of motor and posture, children with cerebral palsy (CP) often have intellectual disability. As a complementary and alternative traditional Chinese medicine (TCM) therapy, Chinese Tuina massage, also called Tuina in China, has been widely applied in clinical treatment for CP in China for a long time. However, the molecular basis for this still remains largely unknown. Recently, DNA hydroxymethylation has been shown to be sensitive to environment and plays critical roles in some neurological disorders, whereas the research focusing on the relationship between 5 hmC and Tuina therapy for cerebral palsy is deficient. In our study, we first observed that Tuina improved learning and memory functions of hypoxic-ischemic (HI) rat pups. Meanwhile, 5 hmC level of the temporal lobe cortex in the HI neonatal rat model is decreased significantly compared to that of the rats in control and Tuina groups. Then, we used the hMeDIP-Seq method to explore whether and how DNA hydroxymethylation is involved in Tuina therapy for cerebral palsy. Genomic annotation of DhMRs of HI group's hypo-hydroxymethylation to genes revealed enrichment in multiple neurodevelopmental signaling pathways. Moreover, we found the depletion of 5 hmC modifications in genes associated with neuronal development was accompanied by reduced mRNA levels of these genes. Taken together, our results indicate that Tuina may regulate the expression of neurodevelopment-related genes by changing the status of DNA hydroxymethylation, thereby improving learning and memory functions of cerebral palsy.

Tuina Massage Improves Cognitive Functions of Hypoxic-Ischemic Neonatal Rats by Regulating Genome-Wide DNA Hydroxymethylation Levels.

Sleep is crucial for proper functioning of the brain, whereas lack of sleep is very common in modern society and can cause memory impairment. Hence, it is of great significance to find effective methods to intervene in the pathogenesis of memory impairment.

Modulation of hippocampal dopamine and synapse-related proteins by electroacupuncture improves memory deficit caused by sleep deprivation.

[This corrects the article DOI: 10.1155/2019/1282085.].

Corrigendum to "Tuina Massage Improves Cognitive Functions of Hypoxic-Ischemic Neonatal Rats by Regulating Genome-Wide DNA Hydroxymethylation Levels".

Alzheimer disease (AD) is a progressive neurodegenerative disease resulting from the accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles. There are currently no objective diagnostic measures for AD. The aim of this study was to identify potential diagnostic markers for AD and evaluate the role of immune cell infiltration in disease pathogenesis. AD expression profiling data for human hippocampus tissue (GSE48350 and GSE5281) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software and the Human Protein Atlas database was used to screen AD-related DEGs. We performed functional enrichment analysis and established a protein-protein interaction (PPI) network to identify disease-related hub DEGs. The fraction of infiltrating immune cells in samples was determined with the Microenvironment Cell Populations-counter method. The random forest algorithm was used to develop a prediction model and receiver operating characteristic (ROC) curve analysis was performed to validate the diagnostic utility of the candidate AD markers. The correlation between expression of the diagnostic markers and immune cell infiltration was also analyzed. A total of 107 AD-related DEGs were screened in this study, including 28 that were upregulated and 79 that were downregulated. The DEGs were enriched in the Gene Ontology terms GABAergic synapse, Morphine addiction, Nicotine addiction, Phagosome, and Synaptic vesicle cycle. We identified 10 disease-related hub genes and 20 candidate diagnostic genes. Synaptophysin () and regulator of G protein signaling 4 () (area under the ROC curve = 0.909) were verified as potential diagnostic markers for AD in the GSE28146 validation dataset. Natural killer cells, B lineage cells, monocytic lineage cells, endothelial cells, and fibroblasts were found to be involved in AD; additionally, the expression levels of both  and  were negatively correlated with the infiltration of these immune cell types. These results suggest that  and  are potential diagnostic markers for AD and that immune cell infiltration plays an important role in AD development and progression.

Article	Year
Genome-Wide Alteration of 5-Hydroxymethylcytosine in Hypoxic-Ischemic Neonatal Rat Model of Cerebral Palsy. Frontiers in molecular neuroscience\| PubMed ID: 31551709	2019
Tuina Massage Improves Cognitive Functions of Hypoxic-Ischemic Neonatal Rats by Regulating Genome-Wide DNA Hydroxymethylation Levels. Evidence-based complementary and alternative medicine : eCAM\| PubMed ID: 31772590	2019
Modulation of hippocampal dopamine and synapse-related proteins by electroacupuncture improves memory deficit caused by sleep deprivation. Acupuncture in medicine : journal of the British Medical Acupuncture Society\| PubMed ID: 32370535	2020
Corrigendum to "Tuina Massage Improves Cognitive Functions of Hypoxic-Ischemic Neonatal Rats by Regulating Genome-Wide DNA Hydroxymethylation Levels". Evidence-based complementary and alternative medicine : eCAM\| PubMed ID: 32454876	2020
Integrated bioinformatics-based identification of diagnostic markers in Alzheimer disease. Frontiers in aging neuroscience\| PubMed ID: 36437991	2022

Danmei Chen

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