Single-Cell Sequencing Technology and Its Application in the Study of Central Nervous System Diseases.

The mammalian central nervous system consists of a large number of cells, which contain not only different types of neurons, but also a large number of glial cells, such as astrocytes, oligodendrocytes, and microglia. These cells are capable of performing highly refined electrophysiological activities and providing the brain with functions such as nutritional support, information transmission and pathogen defense. The diversity of cell types and individual differences between cells have brought inspiration to the study of the mechanism of central nervous system diseases. In order to explore the role of different cells, a new technology, single-cell sequencing technology has emerged to perform specific analysis of high-throughput cell populations, and has been continuously developed. Single-cell sequencing technology can accurately analyze single-cell expression in mixed-cell populations and collect cells from different spatial locations, time stages and types. By using single-cell sequencing technology to compare gene expression profiles of normal and diseased cells, it is possible to discover cell subsets associated with specific diseases and their associated genes. Therefore, scientists can understand the development process, related functions and disease state of the nervous system from an unprecedented depth. In conclusion, single-cell sequencing technology provides a powerful technology for the discovery of novel therapeutic targets for central nervous system diseases.

Effects and mechanisms of salidroside on the behavior of SPS-induced PTSD rats.

Post-traumatic stress disorder (PTSD) is a complex mental disorder, closely associated with stress and traumatic events. Salidroside (Sal) has been reported to possess neuroprotective effects. However, the behavioral effects and mechanisms of Sal on PTSD remain unknown. In this study, we utilized a rat model of PTSD induced by single prolonged stress (SPS) and administered Sal intraperitoneally (25, 50, 75 mg/kg/d) for 14 days. We then examined the behavioral effects and underlying mechanisms of Sal on SPS-induced PTSD rats. Our findings demonstrated that Sal alleviated anxiety-like behavior and spatial learning and memory impairment in SPS-induced PTSD rats. Furthermore, Sal treatment preserved the histomorphology of the hippocampal region. It was observed that Sal protected against hippocampal neuronal apoptosis in PTSD rats by reducing the number of TUNEL-positive cells and modulating apoptosis-related proteins (Bcl-2 and Bax). Additionally, Sal inhibited the activation of the NF-κB/iNOS/COX-2 signaling pathway in the hippocampus of PTSD rats, thereby suppressing the release of inflammatory factors (TNF-α and IL-1ß) and the activation of microglia. Notably, Sal increased the expression of synapse-associated proteins PSD95 and Synapsin I in the hippocampus, while also enhancing dendritic density in the region. In conclusion, our results demonstrated that Sal could attenuate SPS-induced PTSD-like behaviors by inhibiting hippocampal neuronal apoptosis, enhancing hippocampal synaptic plasticity, and reducing neuroinflammatory responses. These findings may provide a foundation for the potential clinical application of Sal in the treatment of PTSD.

Effects and mechanisms of tanshinone IIA on PTSD-like symptoms.

BACKGROUND: In recent years, Salvia miltiorrhiza and its active substances have remarkably progressed in treating central neurological disorders. Tanshinone IIA (TSA) is an active ingredient derived from the rhizome of Salvia miltiorrhiza that has been found to alleviate the symptoms of several psychiatric illnesses. Post-traumatic stress disorder (PTSD) is a mental disorder that results after experiencing a serious physical or psychological injury. The currently used drugs are not satisfactory for the treatment of PTSD. However, it has been reported that TSA can improve PTSD-like symptoms like learning and memory, cognitive disorder, and depression through multi-target regulation. PURPOSE: This paper discusses the ameliorative effects of TSA on PTSD-like symptoms and the possible mechanisms of action in terms of inhibition of neuronal apoptosis, anti-neuroinflammation, and anti-oxidative stress. Based on the pathological changes and clinical observations of PTSD, we hope to provide some reference for the clinical transformation of Chinese medicine in treating PTSD. METHODS: A large number of literatures on tanshinone in the treatment of neurological diseases and PTSD were retrieved from online electronic PubMed and Web of Science databases. CONCLUSION: TSA is a widely studied natural active ingredient against mental illness. This review will contribute to the future development of TSA as a new clinical candidate drug for improving PTSD-like symptoms.

Syntaphilin mediates axonal growth and synaptic changes through regulation of mitochondrial transport: a potential pharmacological target for neurodegenerative diseases.

Mitochondria are a crucial energy source for maintaining neuronal growth and synaptic function. Neurons possess unique morphological characteristics, which make the proper regulation of mitochondrial transport essential for meeting their energy demands. Syntaphilin (SNPH) is capable of specifically targeting the outer membrane of axonal mitochondria, anchoring them to microtubules, and thereby preventing their transport. SNPH also interacts with other mitochondrial proteins to regulate mitochondrial transport. The regulation of mitochondrial transport and anchoring mediated by SNPH is indispensable for axonal growth during neuronal development, maintenance of ATP levels during neuronal synaptic activity, and regeneration of mature neurons following damage. Precise blocking of SNPH may be an effective therapeutic strategy for neurodegenerative diseases and related mental disorders.

The role of RNA splicing factor PTBP1 in neuronal development.

Alternative pre-mRNA splicing, which produces various mRNA isoforms with distinct structures and functions from a single gene, is regulated by specific RNA-binding proteins and is an essential method for regulating gene expression in mammals. Recent studies have shown that abnormal change during neuronal development triggered by splicing mis-regulation is an important feature of various neurological diseases. Polypyrimidine tract binding protein 1 (PTBP1) is a kind of RNA-binding proteins with extensive biological functions. As a well-known splicing regulator, it affects the neuronal development process through its involvement in axon formation, synaptogenesis, and neuronal apoptosis, according to the most recent studies. Here, we summarized the mechanism of alternative splicing, structure and function of PTBP1, and the latest research progress on the role of alternative splicing events regulated by PTBP1 in axon formation, synaptogenesis and neuronal apoptosis, to reveal the mechanism of PTBP1-regulated changes in neuronal development process.

The latest role of nerve-specific splicing factor PTBP1 in the transdifferentiation of glial cells into neurons.

Central nervous system injury diseases can cause the loss of many neurons, and it is difficult to regenerate. The field of regenerative medicine believes that supplementing the missing neurons may be an ideal method for nerve injury repair. Recent studies have found that down-regulation of polypyrimidine tract binding protein 1 (PTBP1) expression can make glial cells transdifferentiate into different types of neurons, which is expected to be an alternative therapy to restore neuronal function. This article summarized the research progress on the structure and biological function of the PTBP family, the mutual regulation of PTBP1 and PTBP2, their role in neurogenesis, and the latest research progress in targeting PTBP1 to mediate the transdifferentiation of glial cells into neurons, which may provide some new strategies and new ideas for the future treatment of central nervous system injury and neurodegenerative diseases. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.

The ameliorative effects and mechanisms of abscisic acid on learning and memory.

Abscisic acid (ABA), a conserved hormone existing in plants and animals, not only regulates blood glucose and inflammation but also has good therapeutic effects on obesity, diabetes, atherosclerosis and inflammatory diseases in animals. Studies have shown that exogenous ABA can pass the blood-brain barrier and inhibit neuroinflammation, promote neurogenesis, enhance synaptic plasticity, improve learning, memory and cognitive ability in the central nervous system. At the same time, ABA plays a crucial role in significant improvement of Alzheimer's disease, depression, and anxiety. Here we review the previous research progress of ABA on the physiological effects and clinical application in the related diseases. By summarizing the biological functions of ABA, we aim to reveal the possible mechanisms of ameliorative function of ABA on learning and memory, to provide a theoretical basis that ABA as a novel and safe drug improves learning memory and cognitive impairment in central system diseases such as aging, neurodegenerative diseases and traumatic brain injury.

The Effects of the Olig Family on the Regulation of Spinal Cord Development and Regeneration.

Neurons and glial cells in the central nervous system (CNS) are generated from neuroepithelial cells in the ventricular zone that surrounds the embryonic neural tube. The proliferation and distinct differentiation of neural precursors occurs at certain stages and are regulated by a series of transcription factors leading to the generation of neuronal and glial cell subtypes. In this manuscript, we review the effects of the Olig family, namely, members Olig1, Olig2 and Olig3, on the distinct differentiation of glial and neuronal cells in the developing spinal cord and injured neural tissue.

Transplantation of NSCs Promotes the Recovery of Cognitive Functions by Regulating Neurotransmitters in Rats with Traumatic Brain Injury.

Transplantation of neural stem cells (NSCs) may be a potential strategy for traumatic brain injury treatment (TBI) due to their intrinsic advantages, such as cell replacement, secretion of neurotrophins and formation of functional synapses with host. However the underlying effects of transplanted NSCs on host micro-environment still need to be further elucidated. In this manuscript the effects of NSCs on release of neurotransmitter, survival of hippocampal neurons, reactivity of astrocytes and recovery of cognitive function after TBI were observed. The NSCs were isolated from cortex of neonatal Sprague-Dawley rat and then transplanted into injured brain regions caused by free-weight drop. The proliferation of astrocytes around injured sites were examined by GFAP immunofluorescent staining on 3, 7, 14 days after injury. The survival of neurons at CA1 regions of hippocampus toward contused regions was observed by HE staining on 3 and 14 days post-injury. The content of glutamic acid (Glu) and GABA in hippocampal tissues was examined on 1, 3, 7, 14, 28 days after injury by ELISA. On third day post-injury, hippocampal-dependent spatial memory was measured for 5 days without intermittent. NSCs in culture have the ability to proliferate and differentiate into different phenotypes of neural cells. After transplantation of NSCs, the proliferation of astrocytes around injured site was significantly inhibited compared to the injured group. At the same time the survival of neurons in hippocampal CA1 region were much more than those in injured group on 14 days post-injury. Meanwhile, the cognitive functions in NSC transplanted group was remarkably improved compared with injured group (p < 0.05). Furthermore, NSCs transplantation dramatically inhibited the release of Glu and maintained the content of GABA in injured hippocampal tissues on 1, 3, 7, 14, 28 days post-injury, which was of difference in statistics (p < 0.05). NSCs transplantation can effectively alleviate the formation of glial scar, enhance the survival of hippocampal neurons and improve cognitive function defects in rats with TBI. The underlying mechanism may be related to their effects on inhibiting the release of Glu and maintaining the content of GABA, so as to down-regulate excitotoxicity of neurotransmitter and improve the micro-environment in injured sites.

[Effect of electroacupuncture on degradation of myosin heavy chain of gastrocnemius muscle in diabetes rats].

OBJECTIVE: To explore the effect of electroacupuncture（EA）on the expression of muscle-specific ring finger protein 1（MuRF1/Trim63），F-box only protein 32（Fbxo32），myosin heavy chain-IIa（Myh2），myosin heavy chain-IIb（Myh4）and myosin heavy chain-I（Myh7）in diabetes rats. METHODS: Thirty-six male Wistar rats were equally randomized into control, model and EA groups. The diabetes model was established by intraperitoneal injection of 0.1% Streptozocin (STZ) solution (50 mg/kg). After that, EA (2 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36), "Yinlingquan" (SP9) and "Shenshu" (BL23) for 10 min, once a day, 6 times a week for 2 weeks. The fasting blood glucose (FBG) and fasting serum insulin (FINS) contents were assayed by using ELISA, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The body weight, and wet weight of bilateral gastrocnemius muscles were measured. The cross-sectional area (CSA) of the gastrocnemius muscle was measured after H.E. stai-ning. The expression of MuRF1, Fbxo32, Myh2, Myh4 and Myh7 mRNAs in the gastrocnemius tissue was tested using quantitative real time-PCR. RESULTS: Compared with the control group, the FBG and HOMA-IR were significantly higher (P<0.05), and the FINS, body weight were significantly lower (P<0.05) after intravenous injection of STZ for 1, 2, 3, 4, 5 weeks respectively. Following EA treatment and compared with the model group, the FBG and HOMA-IR were significantly down-regulated (P<0.05), and the FINS and body weight were considerably increased (P<0.05). Following modeling and compared with the control group, the wet weight of gastrocnemius muscle, CSA, and expression levels of Myh2, Myh4 and Myh7 mRNAs were obviously decreased, and the expression of MuRF1 and Fbxo32 mRNA was obviously increased in the model group (P<0.05). After EA treatment, the gastrocnemius muscle wet weight, CSA, expression levels of Myh2, Myh4 and Myh7 mRNA were significantly up-regulated (P<0.05), and the expression levels of MuRF1 and Fbxo32 mRNA were markedly down-regulated in comparison with those of the model group (P<0.05). CONCLUSION: EA treatment can delay the atrophy of gastrocnemius muscle (skeletal muscle) in diabetes rats possibly by improving the degradation of myosin heavy chain via regulating the expression of muscular MuRF1, Fbxo32, Myh2, Myh4 and Myh7 mRNAs.