• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1189-1196
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• 2023

This study proposed to demonstrate the neuroprotective effects of heat-killed Levilactobacillus brevis KU15152. Heat-killed L. brevis KU15152 showed antioxidant activity similar to that of Lacticaseibacillus rhamnosus GG, in terms of radical scavenging activity. To evaluate the neuroprotective effects, conditioned medium (CM) obtained by incubating heat-killed bacteria in intestinal cells (HT-29) was used through gut-brain axis. CM from L. brevis KU15152 protected neuroblastoma cells (SH-SY5Y) against H₂O₂-induced oxidative stress. Pretreatment with CM significantly alleviated the morphological changes induced by H₂O₂. Heat-killed L. brevis KU15152 showed an increased brain-derived neurotrophic factor (BDNF) expression in HT-29 cells. L. brevis KU15152-CM remarkably downregulated the Bax/Bcl-2 ratio, while upregulating the expression of BDNF and tyrosine hydroxylase (TH) in SH-SY5Y cells. Furthermore, L. brevis KU15152-CM reduced caspase-3 activity following H₂O₂ treatment. In conclusion, L. brevis KU15152 can be potentially used as food materials to avoid neurodegenerative diseases.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.65-76
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• 2024

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.10
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• pp.1398-1406
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• 2016

In general, the seminiferous tubule basement membrane (STBM), comprising laminin, collagen IV, perlecan, and entactin, plays an important role in self-renewal and spermatogenesis of spermatogonial stem cells (SSCs) in the testis. However, among the diverse extracellular matrix (ECM) proteins constituting the STBM, the mechanism by which each regulates SSC fate has yet to be revealed. Accordingly, we investigated the effects of various ECM proteins on the maintenance of the undifferentiated state of SSCs in pigs. First, an extracellular signaling-free culture system was optimized, and alkaline phosphatase (AP) activity and transcriptional regulation of SSC-specific genes were analyzed in porcine SSCs (pSSCs) cultured for 1, 3, and 5 days on non-, laminin- and collagen IV-coated Petri dishes in the optimized culture system. The microenvironment consisting of glial cell-derived neurotrophic factor (GDNF)-supplemented mouse embryonic stem cell culture medium (mESCCM) (GDNF-mESCCM) demonstrated the highest efficiency in the maintenance of AP activity. Moreover, under the established extracellular signaling-free microenvironment, effective maintenance of AP activity and SSC-specific gene expression was detected in pSSCs experiencing laminin-derived signaling. From these results, we believe that laminin can serve as an extracellular niche factor required for the in vitro maintenance of undifferentiated pSSCs in the establishment of the pSSC culture system.

• Molecules and Cells
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• v.27 no.6
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• pp.635-640
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• 2009

Testis-derived germline stem (GS) cells can undergo reprogramming to acquire multipotency when cultured under appropriate culture conditions. These multipotent GS (mGS) cells have been known to differ from GS cells in their DNA methylation pattern. In this study, we examined the DNA methylation status of the H19 imprinting control region (ICR) in multipotent adult germline stem (maGS) cells to elucidate how epigenetic imprints are altered by culture conditions. DNA methylation was analyzed by bisulfite sequencing PCR of established maGS cells cultured in the presence of glial cell line-derived neurotrophic factor (GDNF) alone or both GDNF and leukemia inhibitory factor (LIF). The results showed that the H19 ICR in maGS cells of both groups was hypermethylated and had an androgenetic pattern similar to that of GS cells. In line with these data, the relative abundance of the Igf2 mRNA transcript was two-fold higher and that of H19 was three fold lower than in control embryonic stem cells. The androgenetic DNA methylation pattern of the H19 ICR was maintained even after 54 passages. Furthermore, differentiating maGS cells from retinoic acid-treated embryoid bodies maintained the androgenetic imprinting pattern of the H19 ICR. Taken together these data suggest that our maGS cells are epigenetically stable for the H19 gene during in vitro modifications. Further studies on the epigenetic regulation and chromatin structure of maGS cells are therefore necessary before their full potential can be utilized in regenerative medicine.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.762-768
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• 2020

This study aimed to investigate the effect of ladder-climbing exercise training on neurobiological markers in the hippocampus of mice with type 2 diabetes (T2DM). Twenty-one C57BL/6 male mice were randomly assigned to the non-diabetic control (NDC, n = 7), diabetic control (DC, n = 7), and diabetic training (DT, n = 7) groups. The DT group performed ladder-climbing training (LCT) five times a week for eight weeks. We measured the levels of hippocampal neurobiological markers (catalase [CAT], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], amyloid-beta [Aβ], tau, and CC motif chemokine ligand 11 [CCL11]). The BDNF levels were significantly higher in the DT group than in the DC group (p < 0.05). The Aβ and CCL11 levels were significantly higher in the DC group than in the NDC and DT groups (p < 0.05). The tau levels were significantly higher in the DC group than in the NDC group (p < 0.05). However, there was no significant difference in CAT and NGF levels among the groups (p > 0.05). These results suggest that while T2DM could induce neurodegeneration, LCT may be effective in alleviating neurodegeneration caused by T2DM.

• Nutrition Research and Practice
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• v.10 no.4
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• pp.377-384
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• 2016

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.357-366
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• 2016

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.708-720
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• 2012

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stress-induced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced open-arm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

• Fisheries and Aquatic Sciences
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• v.25 no.8
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• pp.450-461
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• 2022

A randomized, double-blind, and placebo-controlled clinical study was used to determine the cognitive functions related to working memory (WM) and antioxidant properties of fermented Laminaria japonica (FLJ) on healthy volunteers. Eighty participants were divided into a placebo group (n = 40) and FLJ group (n = 40) that received FLJ (1.5 g/day) for 6 weeks. Memory-related blood indices (brain-derived neurotrophic factor, BDNF; angiotensin-converting enzyme; human growth hormone, HGH; insulin-like growth factor-1, IGF-1) and antioxidant function-related indices (catalase, CAT; malondialdehyde, MDA; 8-oxo-2'-deoxyguanosine, 8-oxo-dG; thiobarbituric acid reactive substances, TBARS) were determined before and after the trial. In addition, standardized cognitive tests were conducted using the Cambridge Neuropsychological Test Automated Batteries. Furthermore, the Korean Wechsler Adult Intelligence Scale (K-WAIS)-IV, and the Korean version of the Montreal Cognitive Assessment (MoCA-K) were used to assess the pre and post intake changes on WM-related properties. According to the results, FLJ significantly increased the level of CAT, BDNF, HGH, and IGF-1. FLJ reduced the level of TBARS, MDA, and 8-oxo-dG in serum. Furthermore, FLJ improved physical activities related to cognitive functions such as K-WAIS-IV, MoCA-K, Paired Associates Learning, and Spatial Working Memory compared to the placebo group. Our results suggest that FLJ is a potential candidate to develop functional materials reflecting its capability to induce antioxidant mechanisms together with WM-related indices.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.508-517
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• 2023

In cancer patients, chemo/radio therapy may cause infertility by damaging the spermatogenesis affecting the self-renewal and differentiation of spermatogonial stem cells (SSCs). In vitro differentiation of stem cells especially mesenchymal stem cells (MSCs) into germ cells has recently been proposed as a new strategy for infertility treatment. The aim of this study was to evaluate the proliferation and differentiation of SSCs using their co-culture with Sertoli cells and conditioned medium (CM) from adipose tissue-derived MSCs (AD-MSCs). Testicular tissues were separated from 2-7 days old neonate Wistar Rats and after mechanical and enzymatic digestion, the SSCs and Sertoli cells were isolated and cultured in Dulbecco's modified eagle medium with 10% fetal bovine serum, 1X antibiotic, basic fibroblast growth factor, and glial cell line-derived neurotrophic factor. The cells were treated with the CM from AD-MSCs for 12 days and then the expression level of differentiation-related genes were measured. Also, the expression level of two major spermatogenic markers of DAZL and DDX4 was calculated. Scp3, Dazl, and Prm1 were significantly increased after treatment compared to the control group, whereas no significant difference was observed in Stra8 expression. The immunocytochemistry images showed that DAZL and DDX4 were positive in experimental group comparing with control. Also, western blotting revealed that both DAZL and DDX4 had higher expression in the treated group than the control group, however, no significant difference was observed. In this study, we concluded that the CM obtained from AD-MSCs can be considered as a suitable biological material to induce the differentiation in SSCs.