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1.
Neuroscience Bulletin ; (6): 1625-1636, 2021.
Article in English | WPRIM | ID: wpr-922646

ABSTRACT

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.


Subject(s)
Animals , Cellular Reprogramming , Nerve Regeneration , Neurogenesis , Neuroglia , Neurons
2.
Article in Chinese | WPRIM | ID: wpr-921781

ABSTRACT

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.


Subject(s)
Animals , Depression/drug therapy , Drugs, Chinese Herbal , Growth Differentiation Factors , Hippocampus , Male , Neurogenesis , Proteomics , Rats , Rats, Wistar
3.
Article in Chinese | WPRIM | ID: wpr-888157

ABSTRACT

To analyze the research hotspots and trends of traditional Chinese medicine(TCM) for neurogenesis with use of CiteSpace 5.7.R3 software. The bibliometrics analysis on the literatures of TCM for neurogenesis from 1987 to 2020 included in the CNKI database was conducted to visualize the number of papers, authors, institutions and keywords. Totally 736 literatures were included and the volume of annual publications showed an upward in volatility. At present, several stable research teams have been formed, which were represented by DING Fei, ZHOU Chong-jian and ZHOU Yong-hong, but the cooperation was not close among the teams. According to the analysis of research institutions, Institute of Diagnostics of Hunan University of Chinese Medicine and Acupuncture Research Center of Tianjin University of Traditional Chinese Medicine produced largest number of literatures. The cooperation among institutions, with universities of TCM and affiliated hospitals as the main research force, was characterized by dominant cooperation among regional institutions and less cross-regional cooperation. Keywords analysis showed that in the field of TCM for neurogenesis, a lot of studies mainly focused on the disease field, treatment and medication, TCM therapy and molecular mechanism. The research on TCM therapy and molecular mechanism for neurogenesis of central nervous system will be the research hotspots in future.


Subject(s)
Acupuncture Therapy , Bibliometrics , Databases, Factual , Medicine, Chinese Traditional , Neurogenesis
4.
Article in Chinese | WPRIM | ID: wpr-879853

ABSTRACT

Neural development is regulated by both external environment and internal signals, and in addition to transcription factors, epigenetic modifications also play an important role. By focusing on the genetic mechanism of ATP-dependent chromatin remodeling in children with neurodevelopmental disorders, this article elaborates on the effect of four chromatin remodeling complexes on neurogenesis and the development and maturation of neurons and neuroglial cells and introduces the clinical research advances in neurodevelopmental disorders.


Subject(s)
Child , Chromatin , Chromatin Assembly and Disassembly , Humans , Neurodevelopmental Disorders/genetics , Neurogenesis , Transcription Factors/genetics
5.
Arch. latinoam. nutr ; 70(2): 123-133, jun. 2020. tab, ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-1140336

ABSTRACT

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)


El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)


Subject(s)
Humans , Male , Female , Fish Oils , Fatty Acids, Omega-3 , Oxidative Stress , Alzheimer Disease , Cell Membrane , Chronic Disease , Neurogenesis
6.
Article in Chinese | WPRIM | ID: wpr-879930

ABSTRACT

OBJECTIVE@#To investigate the mechanism of Chinese medicine Buyang Huanwu decoction (BYHWD) promoting neurogenesis and angiogenesis in ischemic stroke rats.@*METHODS@#Male SD rats were randomly divided into sham operation group, model group, BYHWD group, antagonist group and antagonist control group with 14 rats in each. Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery for 90 min with intraluminal filament and reperfusion for 14 d in all groups except sham operation group. BYHWD (13 g/kg) was administrated by gastrogavage in BYHWD group, antagonist group and antagonist control group at 24 h after modeling respectively, and BrdU (50 mg/kg) was injected intraperitoneally in all groups once a day for 14 consecutive days. miR-199a-5p antagomir or NC (10 nmol) was injected into the lateral ventricle at d5 after ischemia in antagonist and antagonist control groups, respectively. The neurological deficits were evaluated by the modified neurological severity score (mNSS) and the corner test, and the infract volume was measured by toluidine blue staining. Neurogenesis and angiogenesis were detected by immunofluorescence double labeling method. The expression level of miR-199a-5p was tested by real-time RT-PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were determined by Western blotting.@*RESULTS@#BYHWD treatment significantly promoted the recovery of neurological function (@*CONCLUSIONS@#Buyang Huanwu decoction promotes neurogenesis and angiogenesis in rats with cerebral ischemia, which may be related to increased protein expression of VEGF and BDNF through upregulating miR-199a-5p.


Subject(s)
Animals , Brain Ischemia/drug therapy , Drugs, Chinese Herbal/therapeutic use , Ischemic Stroke/drug therapy , Male , MicroRNAs/genetics , Neurogenesis/drug effects , Rats , Rats, Sprague-Dawley , Up-Regulation/drug effects , Vascular Endothelial Growth Factor A/genetics
7.
Braz. J. Pharm. Sci. (Online) ; 56: e18772, 2020. tab, graf
Article in English | LILACS | ID: biblio-1285509

ABSTRACT

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer's disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.


Subject(s)
Animals , Male , Mice , Diabetes Mellitus, Type 2/diagnosis , Alzheimer Disease/diagnosis , Risk Factors , Streptozocin/pharmacokinetics , Neurogenesis/genetics , Real-Time Polymerase Chain Reaction/methods
8.
Journal of Rhinology ; : 1-7, 2019.
Article in Korean | WPRIM | ID: wpr-766208

ABSTRACT

The olfactory epithelium is capable of structural and functional recovery after injury through neurogenesis. Neurogenesis occurs via stem cells in the olfactory epithelium. Horizontal basal cells and globose basal cells in the basal layer of the epithelium have the characteristics of stem cells and progenitor cells of olfactory neurons. In order for the horizontal basal cells and globose basal cells to differentiate into olfactory neurons, distinct transcriptional factors are required at each stage. These transcription factors inhibit or synergize with each other or cells at each differentiation stage, regulating olfactory neurogenesis. Recently, the regulation of neurogenesis and development through epigenetic controls that change gene expression without changing the gene sequence have been studied. Studies of olfactory epithelium have helped to elucidate complex neurological systems including spinal cord and brain. In particular, features of neurogenesis will lead to medical advances in the treatment of central nervous diseases, which until this time have been considered impossible.


Subject(s)
Brain , Epigenomics , Epithelium , Gene Expression , Neurogenesis , Neurons , Olfactory Mucosa , Spinal Cord , Stem Cells , Transcription Factors
9.
Article in English | WPRIM | ID: wpr-765324

ABSTRACT

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.


Subject(s)
Alzheimer Disease , Blood-Brain Barrier , Brain , Brain Neoplasms , Essential Tremor , High-Intensity Focused Ultrasound Ablation , Immune System , Magnetic Resonance Imaging , Microbubbles , Models, Animal , Neurodegenerative Diseases , Neurogenesis , Parkinson Disease , Plaque, Amyloid , Sonication , Therapeutic Uses , Transducers , Ultrasonography , United States Food and Drug Administration
10.
Article in English | WPRIM | ID: wpr-719412

ABSTRACT

Neural stem cells (NSCs) can proliferate and differentiate into multiple cell types that constitute the nervous system. NSCs can be derived from developing fetuses, embryonic stem cells, or induced pluripotent stem cells. NSCs provide a good platform to screen drugs for neurodegenerative diseases and also have potential applications in regenerative medicine. Natural products have long been used as compounds to develop new drugs. In this review, natural products that control NSC fate and induce their differentiation into neurons or glia are discussed. These phytochemicals enable promising advances to be made in the treatment of neurodegenerative diseases.


Subject(s)
Biological Products , Embryonic Stem Cells , Fetus , Induced Pluripotent Stem Cells , Nervous System , Neural Stem Cells , Neurodegenerative Diseases , Neurogenesis , Neuroglia , Neurons , Neuroprotection , Phytochemicals , Regenerative Medicine
11.
Article in English | WPRIM | ID: wpr-772943

ABSTRACT

N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.


Subject(s)
Adenosine , Metabolism , Adult Stem Cells , Cell Biology , Metabolism , Animals , Brain , Metabolism , Cell Differentiation , Genetics , Cell Proliferation , Enhancer of Zeste Homolog 2 Protein , Metabolism , Gene Expression Regulation , Methyltransferases , Metabolism , Mice, Inbred C57BL , Neural Stem Cells , Cell Biology , Metabolism , Neurogenesis , Genetics , Neurons , Cell Biology , Metabolism , RNA, Messenger , Genetics , Metabolism
12.
Article in English | WPRIM | ID: wpr-763527

ABSTRACT

OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.


Subject(s)
Cognition , Depression , Fruit , Garcinia mangostana , Garcinia , Inflammation , Neurogenesis , Outcome Assessment, Health Care , Oxidation-Reduction , Oxidative Stress , Psychopathology , Psychotic Disorders , Schizophrenia , Synaptic Transmission , Xanthones
13.
Experimental Neurobiology ; : 229-246, 2019.
Article in English | WPRIM | ID: wpr-739542

ABSTRACT

Neural stem cells (NSCs) have the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes. Highly dynamic nature of NSC differentiation requires the intimate involvement of catabolic processes such as autophagy. Autophagy is a major intracellular degradation pathway necessary for cellular homeostasis and remodeling. Autophagy is important for mammalian development and its role in neurogenesis has recently drawn much attention. However, little is known about how autophagy is associated with differentiation of NSCs into other neural lineages. Here, we report that autophagy plays a critical role in differentiation of adult rat hippocampal neural stem (HCN) cells into astrocytes. During differentiation, autophagy flux peaked at early time points, and remained high. Pharmacological or genetic suppression of autophagy by stable knockdown of Atg7, LC3 or CRISPR-Cas9-mediated knockout (KO) of p62 impaired astrogenesis, while reintroduction of p62 recovered astrogenesis in p62 KO HCN cells. Taken together, our findings suggest that autophagy plays a key role in astrogenesis in adult NSCs.


Subject(s)
Adult Stem Cells , Adult , Animals , Astrocytes , Autophagy , Cell Differentiation , Homeostasis , Humans , Neural Stem Cells , Neurogenesis , Neurons , Oligodendroglia , Rats , Suppression, Genetic
14.
Article in English | WPRIM | ID: wpr-788753

ABSTRACT

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.


Subject(s)
Alzheimer Disease , Blood-Brain Barrier , Brain , Brain Neoplasms , Essential Tremor , High-Intensity Focused Ultrasound Ablation , Immune System , Magnetic Resonance Imaging , Microbubbles , Models, Animal , Neurodegenerative Diseases , Neurogenesis , Parkinson Disease , Plaque, Amyloid , Sonication , Therapeutic Uses , Transducers , Ultrasonography , United States Food and Drug Administration
15.
Article in English | WPRIM | ID: wpr-785836

ABSTRACT

Space traveling is imperative for mankind in the future. Expectedly, hibernation will become an option for space traveler to overcome the endless voyage. With regard to some of the studies pointed out that during hibernation, muscle will undergo atrophy and meantime neurogenesis will reduce, these obstacles were frequently related with stem cell regeneration. Thus, investigation on whether hibernation will lead to dysfunction of stem cell becomes an important issue. By going through four main systems in this article, such as, hematopoietic system, skeletal muscle system, central nervous system and orthopedic system, we are expecting that stem cells regeneration capacity will be affected by hibernation. To date, these researches are majorly the read-out from short term or seasonal hibernating mammals. Proposing and creating a simulated long-term hibernation animal model is turning essential for the further investigation on the effect of longer period of hibernation to human stem cells.


Subject(s)
Adult Stem Cells , Adult , Arousal , Atrophy , Central Nervous System , Hematopoietic System , Hibernation , Humans , Mammals , Models, Animal , Muscle, Skeletal , Neurogenesis , Orthopedics , Regeneration , Seasons , Stem Cells , Torpor
16.
Article in English | WPRIM | ID: wpr-785827

ABSTRACT

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis and neuronal development. Intrigued we tested the possibility that PSMD10(Gankyrin) may be strongly associated with cell fate decisions that commit neural stem cells to differentiate into neurons. Overexpression of PSMD10(Gankyrin) in human neural progenitor cells facilitated neuronal differentiation via β-catenin Ngn1 pathway. Here for the first time we provide preliminary and yet compelling experimental evidence for the involvement of a potential oncoprotein – PSMD10(Gankyrin), in neuronal differentiation.


Subject(s)
HEK293 Cells , Humans , Neural Stem Cells , Neurogenesis , Neurons , Proteasome Endopeptidase Complex , Stem Cells , Transcriptome
17.
Article in English | WPRIM | ID: wpr-764113

ABSTRACT

PURPOSE: Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal–regulated kinases (MEK)/extracellular signal–regulated kinases (ERK) pathways in the hippocampus. METHODS: Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. RESULTS: The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. CONCLUSIONS: Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.


Subject(s)
Abdominal Wall , Adenosine Monophosphate , Blotting, Western , Castration , Cyclic AMP-Dependent Protein Kinases , Down-Regulation , Goserelin , Hippocampus , Immunohistochemistry , Memory , Memory, Short-Term , Models, Animal , Neurogenesis , Orchiectomy , Phosphorylation , Phosphotransferases , Spatial Memory
18.
Laboratory Animal Research ; : 203-210, 2018.
Article in English | WPRIM | ID: wpr-718848

ABSTRACT

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.


Subject(s)
Adult , Animals , Cell Proliferation , Cilia , Dentate Gyrus , Hippocampus , Homeostasis , Humans , Mice , Neurogenesis , Neurons , Organelles
19.
Laboratory Animal Research ; : 239-247, 2018.
Article in English | WPRIM | ID: wpr-718843

ABSTRACT

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.


Subject(s)
Animals , Bacopa , Blotting, Western , Brain-Derived Neurotrophic Factor , Cell Proliferation , Cognition Disorders , Cyclic AMP Response Element-Binding Protein , Dentate Gyrus , Discrimination, Psychological , Immunohistochemistry , Memory , Mice , Neurogenesis , Phosphorylation , Plants, Medicinal
20.
Article in English | WPRIM | ID: wpr-717678

ABSTRACT

PURPOSE: Mesenchymal stem cells (MSCs) have demonstrated great promises for the treatment of ischemic stroke. Previously, we identified a new source of MSCs located in the inferior turbinate. We investigated therapeutic potentials of human turbinate- derived mesenchymal stem cells (hTMSCs) in ischemic stroke. METHODS: Ischemic stroke was induced by the intraluminal occlusion of middle cerebral artery (MCAo) for 50 minutes in rats. At one day after MCAo, hTMSCs, adipose tissue-derived MSCs (AdMSCs), or phosphate buffered saline (PBS) were transplanted into the striatum. Functional recovery was assessed by repeating behavioral tests including modified neurologic severity score and corner test. At 14 days after MCAo, brains were stained with hematoxylin and eosin (H&E) for measuring infarct volume. The survival of grafted MSCs was evaluated by immunohistochemistry to human nuclei (hNU). Immunohistochemistry with anti-doublecortin (anti-DCX) was performed to assess hippocampal neurogenesis. RESULTS: Transplantation of hTMSCs following MCAo showed improvements of neurologic function, which was comparable with that of AdMSCs. H&E staining showed no difference in infarct volume among 3 groups. Regarding the survival of grafted MSCs, the number of hNU-expressing cells was not different between hTMSCs- and AdMSCs-treated groups. Finally, hTMSCs increased the number of subgranular DCX-positive cells compared to PBS-treated controls, without affecting hilar ectopic migration of newborn neurons. CONCLUSIONS: hTMSCs could improve functional recovery following ischemic stroke, of which efficacy was similar to AdMSCs. Although hTMSCs showed comparable infarct size and survival of grafted MSCs, transplantation of hTMSCs could upregulate subgranular neurogenesis with no impact on ectopically migrating newborn neurons.


Subject(s)
Animals , Behavior Rating Scale , Brain , Eosine Yellowish-(YS) , Hematoxylin , Humans , Immunohistochemistry , Infant, Newborn , Mesenchymal Stem Cells , Middle Cerebral Artery , Neurogenesis , Neurons , Rats , Stroke , Transplantation , Transplants , Turbinates
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