Myung Sook Oh’s research while affiliated with Kyung Hee University and other places

Background/Objectives: Parkinson’s disease (PD) is a common neurodegenerative disease characterized by motor symptoms caused by the loss of dopaminergic neurons. While the pathophysiology of PD is still not fully understood, it is recognized that oxidative stress plays a major role in its progression. Previous studies have shown that the aerial parts of Artemisia iwayomogi Kitamura (AIK) possess medicinal properties, including antioxidant activity. This study aimed to investigate whether AIK can alleviate neuronal loss and motor symptoms in a PD model and to explore its therapeutic mechanisms. Methods: For the in vitro study, PC12 cells were treated with AIK and 1-methyl-4-phenylpyridinium (MPP+). For the in vivo study, C57BL/6J mice were orally administered AIK for 12 days; they received intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 consecutive days, starting on the 8th day of AIK administration. Results: AIK treatment to PC12 cells in the presence of MPP+ enhanced the phosphorylation of the protein kinase B/glycogen synthase kinase-3β signaling pathway, which is a crucial regulator of nuclear factor erythroid 2-related factor 2 (Nrf2) translocation. Additionally, AIK treatment increased cell survival and induced an antioxidant response involving heme oxygenase-1, via increasing the level of Nrf2 in the nucleus. In an MPTP-induced mouse model of PD, AIK administration activated Nrf2 in dopaminergic neurons and prevented the loss of dopaminergic neurons in the brain, which in turn alleviated motor dysfunction. Conclusions: Collectively, these findings suggest that AIK is a potential botanical candidate for PD treatment by protecting dopaminergic neurons through antioxidant activity.

Parkinson’s disease (PD) affects 1–2% of the global population and presents significant therapeutic challenges. Due to the limitations of existing treatments, there is a pressing need for alternative approaches. This study investigated the effects of invasive laser acupuncture (ILA), which combines acupuncture and photobiomodulation. In this method, optical fibers are inserted into the muscle layers of the acupoint to enhance therapeutic outcomes. Mice with MPTP-induced PD were treated with ILA at 830 nm or 650 nm. Protective effects of nigrostriatal dopaminergic neurons and fibers were assessed by examining TH immunoreactivity in the brain. Neuroinflammation markers in the brain and muscle metabolomic profiles were also analyzed. Comparisons between invasive and non-invasive laser application, as well as the impact of nerve blocking with lidocaine, were also evaluated. ILA at 830 nm (ILA830) significantly improved motor performance and increased the nigrostriatal TH-positive immunoreactivities. It reduced the levels of α-synuclein, apoptotic proteins, and inflammatory cytokines, while increasing anti-inflammatory in the brain. ILA830 also decreased nigrostriatal astrocyte and microglia activation. Muscle metabolomic analysis showed distinct group clustering and significant changes in metabolites like glucose and galactose, correlating with improved motor functions. Invasive laser treatment was more effective than non-invasive, and lidocaine pre-treatment did not block its effects. ILA at 830 nm effectively ameliorates PD symptoms by protecting dopaminergic neurons, and reducing neuroinflammation in the brain. Muscle metabolomic changes by ILA830, such as increased glucose and galactose, correlate with motor improvement. This approach offers a promising strategy for PD treatment, warranting further research to optimize its use in clinical settings.

Purpose Parkinson's disease (PD) disrupts the regulation of neurotransmitters in the brain, causing patients to experience not only motor symptoms but also non-motor symptoms such as depression. 6-shogaol (6S) is a potential neuro-nutraceutical derived from ginger, and is known to ameliorate motor symptoms by suppressing inflammation in PD mice. In this study, we investigated whether 6S can attenuate motor symptoms and depression-like behaviors through neurotransmitter regulation and to elucidate which neurotransmitters are intimately correlated with these effects. Methods C57BL/6 J mice were injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 d to induce PD. 6S was administered via oral gavage for 11 d, including the MPTP injection period. Results 6S alleviated MPTP-induced motor symptoms and depression-like behaviors. MPTP injection decreased the levels of seven neurotransmitters in the striatum and four neurotransmitters in the hippocampus. Administration of 6S increased striatal dopamine, serotonin, and norepinephrine levels and hippocampal dopamine, norepinephrine, serotonin, and γ-aminobutyric acid levels. Moreover, correlation analysis shown that the motor symptom improvement effect of 6S was associated with striatal dopamine, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels. The effect of 6S on depressive-like behavior was significantly correlated with striatal dopamine metabolites and serotonin and hippocampal dopamine, norepinephrine, and serotonin. Immunohistochemistry showed that 6S upregulated the expression of the vesicular monoamine transporter 2, which was reduced by MPTP in the striatum and hippocampus. Conclusion This study demonstrated that 6S improved motor symptoms and depression-like behaviors by regulating the release of monoamine neurotransmitters.

Tauopathy is widely observed in multiple neurodegenerative diseases such as Alzheimer’s disease (AD) and characterized by abnormal tau protein phosphorylation, aggregation and its accumulation as a form of neurofibrillary tangle (NFT) in the brain. However, there are no effective treatments targeting tau pathology in the AD. Vitamin C is known to reduce tauopathy and modulate one of its regulators called glycogen synthase kinase 3 (GSK3) in the body. Nevertheless, vitamin C has a limitation of its stability during metabolism due to its chemical properties. Thus, in the current study, NXP032 (a vitamin C/aptamer complex) was tested as a candidate for tau-targeting treatment because it can preserve antioxidative efficacy of vitamin C before it can reach the target tissue. In this context, the current study aimed to investigate the therapeutic effect of NXP032 on tauopathy in vivo and in vitro. As a result, NXP032 attenuated cognitive and memory decline and reduced NFT and tau hyperphosphorylation in the P301S mutant human tau transgenic mice (or called PS19 mice). In addition, NXP032 suppressed neuroinflammation found in the PS19 mice. Furthermore, NXP032 protected SH-SY5Y human neuroblastoma cells from okadaic acid (OKA)-induced cytotoxicity. Especially, 10 ng/ml of NXP032 reduced tau hyperphosphorylation and GSK3 activation though its phosphorylation at Tyr216 site which were promoted by OKA treatment in the SH-SY5Y cells. Taken together, our results suggest that NXP032 might be a potential therapy for AD and tauopathy-related neurodegenerative disorders as well. Graphical Abstract

We developed a reversed-phased high-performance liquid chromatographic method combining ultraviolet detection and integrated pulsed amperometric detection for the simultaneous quantification of dopamine, 5-hydroxyindolacetic acid, homovanillic acid, serotonin, 3,4-dihydroxyphenylacetic acid, norepinephrine and epinephrine. All target components were completely separated in a C18 column with isocratic elution of 5% acetonitrile solution containing 8 mM HClO4 and 0.20 mM 1-octanesulfonic acid as an ion pairing reagent. This method showed limits of detection of 0.03–0.1 ng and limits of quantification of 0.10–0.3 ng with linear regression coefficients of 0.9998–1.0000. All inter-day and intra-day precision values were below 9.58%, and the average recoveries were 93.71–109.82% for mouse striatum samples. The mean levels of the seven components in striatal brain tissue in a mouse model of Parkinson’s disease decreased by 2–12 times compared to those of a control group. In particular, the decrease in dopamine, 5-hydroxyindolacetic acid and 3,4-dihydroxyphenylacetic acid was statistically significant (P < 0.05). Orthogonal partial least squares discriminant analysis confirmed that the seven components are useful biomarkers. The significance of the developed method lies in its ability to simultaneously analyze seven biogenic amines related to Parkinson’s disease by combining two detectors, offering a simple and cost-effective approach for clinical and biological labs.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. In particular, neuroinflammation associated with phosphorylation of c-Jun N-terminal kinase (JNK) is likely to cause the death of dopaminergic neurons. Therefore, protecting dopaminergic neurons through anti-neuroinflammation is a promising therapeutic strategy for PD. This study investigated whether Tribuli Fructus (TF) could alleviate PD by inhibiting neuroinflammation. Mouse primary mixed glial culture cells from the mouse cortex were treated with lipopolysaccharide (LPS) to induce neuroinflammation, and 1 h later, cells were treated with TF. 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was injected into C57BL/6J mice for 5 days, and TF was co and post-administered for 12 days. Our study showed that TF attenuated pro-inflammatory mediators and cytokines in LPS-stimulated primary mixed glial cultures. In the brains of MPTP-induced PD mouse model, TF inhibited the activation of microglia and astrocytes, protected dopaminergic neurons, and increased dopamine levels. TF alleviated MPTP-induced bradykinesia, a representative behavioral disorder in PD. In addition, the results in vitro and in vivo revealed that TF regulates the phosphorylation of JNK. Collectively, our data suggest that TF may be a new therapeutic candidate for PD by regulating JNK signaling.

Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of the structure and function of the nervous system, represent a significant global health challenge. Emerging research suggests that the gut microbiota plays a critical role in regulating neurodegeneration via modulation of the gut-brain axis. Probiotics, defined as live microorganisms that confer health benefits to the host, have garnered significant attention owing to their therapeutic potential in NDDs. This review examines the current research trends related to the microbiome-gut-brain axis across various NDDs, highlighting key findings and their implications. Additionally, the effects of specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus rhamnosus, on neurodegenerative processes were assessed, focusing on their potential therapeutic benefits. Overall, this review emphasizes the potential of probiotics as promising therapeutic agents for NDDs, underscoring the importance of further investigation into this emerging field.

Donepezil (DNZ) has been used to treat dementia associated with mild, moderate, or severe Alzheimer's disease (AD). DNZ uptake can alleviate cognitive symptoms in AD patients via acetylcholinesterase (AChE) inhibition....

Background Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear. Results We investigated the effect of MGO stress on depression like-behavior and memory loss to elucidate the potential interplay between MGO-induced tryptophan (Trp) metabolism impairment and oxidative stress in the brain. It demonstrates that MGO induces depression-like behavior in mice, as confirmed by the OFT, TST, FST, SPT, and EPM behavioral tests. MGO led to the depletion of Trp and related neurotransmitters as 5-HT, EPI, and DA in the mouse brain. Additionally, MGO reduced the cell count in the DG, CA1, and CA3 hippocampal regions and modulated TPH2 levels in the brain. Notably, co-treatment with MGO and Trp mirrored the effects observed after Trp-null treatment in neurons, including reduced TPH1 and TPH2 levels and inhibition of neuronal outgrowth. Furthermore, MGO significantly altered the expression of key proteins associated with neurodegeneration, such as p-Tau, p-GSK-3β, APP, oAβ, BDNF, NGF, and p-TrkB. Concurrently, MGO activated MAPKs through ROS induction, triggering a redox imbalance by downregulating Nrf-2, Ho-1, TXNRD1, Trx, Sirt-3, and Sirt-5 expression levels, NAD+, and CAT activity in the mouse brain. This led to an accelerated neuroinflammatory response, as evidenced by increased expression of Iba-1, p-NF-κB, and the secretion of IL-6 and TNF-α. Importantly, Trp treatment ameliorated MGO-induced depression like-behavior and memory loss in mice and markedly mitigated increased expression of p-Tau, APP, p-ERK1/2, p-pJNK, and p-NF-κB in the brain. Likewise, Trp treatment also induced the expression of MGO detoxifying factors GLO-I and GLO-II and CAT activity, suggesting the induction of an antioxidant system and reduced inflammation by inhibiting IL-6 and TNF-α secretion. Conclusions Our data revealed that MGO-induced depression like-behavior and memory deficits resulted from disturbances in Trp, 5-HT, BDNF, and NGF levels, increased p-Tau and APP expression, neuroinflammation, and impaired redox status (Nrf-2/Ho-1/TXNRD1/Sirt3/5) in the brain. Supplementary Information The online version contains supplementary material available at 10.1186/s40659-024-00572-4.

Introduction Immune dysfunction is a major cause of neuroinflammation and accelerates the progression of Parkinson’s disease (PD). Numerous studies have shown that stimulation of specific acupuncture points (acupoints) can ameliorate PD symptoms. The purpose of this study was to investigate whether attaching microneedles to acupoints would improve PD pathology by recovering immune dysfunction. Methods The PD mouse model was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), and microneedle patches (MPs) or sham patches (SPs) were attached to GB20 and GB34, representative acupoints for treating PD for 14 days. Results First, the behavioral experiment showed that motor disorders induced by 6-OHDA were significantly improved by MP. Simultaneously, 6-OHDA-induced dopaminergic neuronal death and brain neuroinflammation decreased. Conversely, SP had no effect on behavioral disorders, neuronal death, or neuroinflammation. Measurement results from flow cytometry of immune cells in the brain and blood revealed a disruption in the CD4+/CD8+ ratio in the 6-OHDA group, which was significantly restored in the MP group. The brain mRNA expression of cytokines was significantly increased in the 6-OHDA group, which was significantly decreased by MP. Discussion Overall, our results suggest that the attachment of MPs to GB20 and GB34 is a new method to effectively improve the pathology of PD by restoring peripheral and brain immune function.