• Anatomy and Cell Biology
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• v.56 no.2
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• pp.219-227
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• 2023

Adult neurogenesis has been reported in the hypothalamus, subventricular zone and subgranular zone in the hippocamp. Recent studies indicated that new cells in the hypothalamus are affected by diet. We previously showed beneficial effects of safflower seed oil (SSO), a rich source of linoleic acid (LA; 74%), on proliferation and differentiation of neural stem cells (NSCs) in vitro. In this study, the effect of SSO on hypothalamic neurogenesis was investigated in vivo, in comparison to synthetic LA. Adult mice were treated with SSO (400 mg/kg) and pure synthetic LA (300 mg/kg), at similar concentrations of LA, for 8 weeks and then hypothalamic NSCs were cultured and subsequently used for Neurosphere-forming assay. In addition, serum levels of brain-derived neurotrophic factor (BNDF) were measured using enzyme-linked immunosorbent assay. Administration of SSO for 8 weeks in adult mice promoted the proliferation of NSCs isolated from SSO-treated mice. Immunofluorescence staining of the hypothalamus showed that the frequency of astrocytes (glial fibrillary acidic protein⁺ cells) are not affected by LA or SSO. However, the frequency of immature (doublecortin⁺ cells) and mature (neuronal nuclei⁺ cells) neurons significantly increased in LA- and SSO-treated mice, compared to vehicle. Furthermore, both LA and SSO caused a significant increase in the serum levels of BDNF. Importantly, SSO acted more potently than LA in all experiments. The presence of other fatty acids in SSO, such as oleic acid and palmitic acid, suggests that they could be responsible for SSO positive effect on hypothalamic proliferation and neurogenesis, compared to synthetic LA at similar concentrations.

• The Korean Journal of Applied Statistics
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• v.31 no.3
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• pp.417-426
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• 2018

An alternative developmental toxicity test using mouse embryonic stem cell derived embryoid bodies has been developed. This alternative method is not to administer chemicals to animals, but to treat chemicals with cells. This study suggests the use of Discriminant Analysis, Support Vector Machine, Artificial Neural Network and k-Nearest Neighbor. Algorithm performance was compared with accuracy and a weighted Cohen's kappa coefficient. In application, various classification techniques were applied to cytotoxicity data to classify drug toxicity and compare the results.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.12 no.7
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• pp.1243-1248
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• 2008

As development in technology of bioinformatics recently mates it possible to operate micro-level experiments, we can observe the expression pattern of total genome through on chip and analyze the interactions of thousands of genes at the same time. In this thesis, we used CDNA microarrays of 3840 genes obtained from neuronal differentiation experiment of cortical stem cells on white mouse with cancer. It analyzed and compared performance of each of the experiment result using existing DT, NB, SVM and multi-perceptron neural network classifier combined the similar scale combination method after constructing class classification model by extracting significant gene list with a similar scale combination method proposed in this paper through normalization. Result classifying in Multi-Perceptron neural network classifier for selected 200 genes using combination of PC(Pearson correlation coefficient) and ED(Euclidean distance coefficient) represented the accuracy of 98.84%, which show that it improve classification performance than case to experiment using other classifier.

• Food Science and Preservation
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• v.24 no.4
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• pp.524-528
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• 2017

Ricinus communis, belongs to the family Euphorbiaceae, has been known as medicinal plants for treatment of inflammation, tumors, antidiabetic, hepatoprotective and laxative. Compared to many pharmacological studies, the effect of R. communis extract on regulating adipogenesis as therapeutic drug for treating obesity has not been reported. R. communis extract (RCE) was investigated to determine its effects on the adipogenesis by monitoring the status of $Wnt/{\beta}-catenin$ signaling and factors involving the differentiation of adipocytes. The differentiation of 3T3-L1 cells monitored by Oil Red O staining was inhibited in concentration dependent manner by RCE. The luciferase activity of HEK 293-TOP cells containing pTOPFlash with Tcf4 response element-luciferase gene was increased approximately 2-folds by the treatment of RCE at concentrations of $100{\mu}g/mL$ compared to the control. Activation of the $Wnt/{\beta}-catenin$ pathway by RCE was further confirmed by immunocytochemical analysis which shows an increment of nuclear localization of ${\beta}-catenin$. In addition, safety of RCE was verified through performing neural stem cell morphology assay. Among the identified flavonoids in RCE, isoquercitrin was the most abundant. Therefore, these results indicate that the adipocyte differentiation was significantly reduced by isoquercitrin in R. communis. In this study, RCE suppresses the adipogenesis of 3T3-L1 cells via the activation of $Wnt/{\beta}-catenin$ signaling.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• BMB Reports
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• v.57 no.6
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• pp.281-286
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• 2024

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

• Molecules and Cells
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• v.39 no.8
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• pp.603-610
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• 2016

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.

• Development and Reproduction
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• v.17 no.3
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• pp.179-186
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• 2013

Neural stem cells are found in adult mammalian brain regions including the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ). In addition to these two regions, other neurogenic regions are often reported in many species. Recently, the subcallosal zone (SCZ) has been identified as a novel neurogenic region where new neuroblasts are spontaneously generated and then, by Bax-dependent apoptosis, eliminated. However, the development of SCZ in the postnatal brain is not yet fully explored. The present study investigated the precise location and amount of neuroblasts in the developing brain. To estimate the importance of programmed cell death (PCD) for SCZ histogenesis, SCZ development in the Bax-knockout (KO) mouse was examined. Interestingly, an accumulation of extra neurons with synaptic fibers in the SCZ of Bax-KO mice was observed. Indeed, Bax-KO mice exhibited enhanced startle response to loud acoustic stimuli and reduced anxiety level. Considering the prevention of PCD in the SCZ leads to sensory-motor gating dysfunction in the Bax-KO mice, active elimination of SCZ neuroblasts may promote optimal brain function.

• Korean Journal of Plant Resources
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• v.29 no.5
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• pp.620-624
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• 2016

The Wnt/β-catenin signaling pathway is mandatory in adipogenesis. In this study, we investigated the applicability of functional materials for the treatment of obesity by examining Wnt/β-catenin pathway reporter activity related to adipocyte differentiation inhibiting with korean native plant extracts. The luciferase activity of HEK 293-TOP cells increased the reporter activity approximately 152% and 130% by treatment with Sanguisorba officinalis and Thuja orientalis, respectively. Ricinus communis were represented about 90% higher activity, two samples(Rosa rugosa and Sophorae Flos) showed 80% higher activity than the control. Three samples of plant extracts (Zanthoxylum piperitum, Pueraria thunbergiana, Solanum nigrum) were about 70% higher activity compared with the non-treated control. Cytotoxicity of plant extracts was not detected in the rat neural stem cells. These results suggest that the selected eight plant extracts are safe compounds. Our findings indicate that Wnt/β-catenin pathway reporter activity could be used for high throughput screening system. In addition, the plant extracts selected as candidates for adipocyte differentiation inhibiting may be potential therapeutic agents for obesity, it will be exploring the possibility of developing an anti-obesity materials through further experiments with selected plant extracts.

• Molecules and Cells
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• v.45 no.9
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• pp.640-648
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• 2022

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and pan-neuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.