• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.166-174
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• 2019

Objective : Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson's disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. Methods : Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. Results : Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. Conclusion : Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.178-184
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• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.363-372
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• 2019

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.133-139
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• 2021

Objectives : Parkinson's disease is a neurodegenerative disease caused by a decrease in the dopaminergic neurons in the substantia nigra. The abnormal expression of solute carrier family 6 member 4 (Slc6a4) has been reported in patients with Parkinson's disease. Methods : In this study, we used MPTP to examine the changes in the expression of Slc6a4 in the brain of mice with Parkinson's disease and investigate its effect on dopaminergic neuronal cell death. Results : In the examination of the Slc6a4 expression in the substantia nigra of MPTP-treated mice for 4 weeks. The gene expression was increased compared to the normal group. To investigate the relationship between Slc6a4 and dopaminergic neurons, we performed a study using siRNA of Slc6a4 in the dopaminergic neuronal cell line SH-SY5Y. Using the siRNA of Slc6a4 to evaluate gene expression, it revealed that the tyrosine hydroxylase (TH) expression increases when Slc6a4 decreases. Moreover, this confirms its effects on the dopaminergic neurons. Additionally, through the evaluation of factors related to apoptosis, in particular, it was established that the value of bax/bcl2 decreased and was affected. These results suggest that a decreased Slc6a4 expression induces an increase in TH expression, providing a mechanism of action for dopaminergic neurons regulated by Slc6a4 expression. Conclusions : Slc6a4 is deemed to be involved in the regulation of dopaminergic neurons, suggesting that an increased Slc6a4 expression induced by MPTP may influence a reduction of dopaminergic neurons.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.1089-1099
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• 2020

Objective: The purpose of this study was to investigate the effect of cinnamon on the treatment of Parkinson's disease (PD) and to introduce its use in Korea. Method: We searched the experimental studies in electronic databases (PubMed, CNKI, Wanfang, CiNii, J-STAGE, Science ON, and OASIS) using the key search terms "cinnamic acid", "cinnamon", "cinnamomum", "Parkinson's disease", "Parkinson disease", "Parkinsonism", and "dopamine". This study only involved experimental studies (in vivo and in vitro) that adopted cinnamon as a single administration and measured indicators relating to Parkinson's disease, including parkin, tyrosine hydroxylase (TH), and dopamine. Results: A Total of 11 literature studies were selected, and they all showed that treatment with cinnamon has a neuroprotective effect. Cinnamon activated neuroprotective factors and restored neurotransmitters and it reduced the rate of oxidative stress and inflammation in neurons. As a result, cell viability was upregulated, while cell apoptosis and neurodegeneration were downregulated. Five in vivo studies, through behavioral tests, also confirmed that cinnamon recovers locomotor function in PD models. Conclusion: We identified that cinnamon is an effective neural protector and improves motor performance in behavioral testing in the experimental PD studies.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.9-16
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• 2014

Objectives : Investigation of the antidepressant effect of Glycyrrhizae Radix (GR) through the anti-inflammatory effect. Methods : Depression in rats was induced by LPS (i,p.3days). The rats were treated with GR100 mg/kg (GR 100) or GR400 mg/kg (GR 400). The depressive immobility was examined with Tail Suspension Test(TST) and Forced Swimming Test(FST). The expression of nuclear factor-${\kappa}B$(NF-${\kappa}B)$, $I{\kappa}B$ was measured with western blotting. The concentration of corticosterone, cytokine in plasma was measured with ELISA. The expression of c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coeluleus(LC) were measured with immunostaining method. Results : In the TST, GR400 group significantly decreased immobility time compared with the LPS group. In the FST, GR100, GR400 group significantly decreased immobility time comparing with the LPS group. c-Fos expression in GR100 and GR400 group was decreased comparing with the lipoplysaccharide(LPS) group. The $I{\kappa}B$ expression of GR100 and GR400 group was increased comparing with the LPS group. The level of corticosterone of GR100 group was decreased comparing with the LPS group. The concentration of cytokine of GR100 and GR400 group was decreased comparing with the LPS group. TH expression in the LC was increased in LPS group, but in GR100 and GR400 group was not shown significant decrease. Conclusion : According to this results obtained, GR has antidepressant effects by the anti inflammatory action through the suppression of HPA axis activity, not through the action against the catecholaminergic system.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• 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.

• BMB Reports
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• v.56 no.3
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• pp.202-207
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• 2023

We investigated the neuroprotective effects of deca nano-graphene oxide (daNGO) against reactive oxygen species (ROS) and inflammation in the human neuroblastoma cell line SH-SY5Y and in the 6-hydroxydopamine (6-OHDA) induced Parkinsonian rat model. An MTT assay was performed to measure cell viability in vitro in the presence of 6-OHDA and/or daNGO. The intracellular ROS level was quantified using 2',7'-dichlorofluorescein diacetate. daNGO showed neuroprotective effects against 6-OHDA-induced toxicity and also displayed ROS scavenging properties. We then tested the protective effects of daNGO against 6-OHDA induced toxicity in a rat model. Stepping tests showed that the akinesia symptoms were improved in the daNGO group compared to the control group. Moreover, in an apomorphine-induced rotation test, the number of net contralateral rotations was decreased in the daNGO group compared to the control group. By immunofluorescent staining, the animals in the daNGO group had more tyrosine hydroxylase-positive cells than the controls. By anti-Iba1 staining, 6-OHDA induced microglial activation showed a significantly decrease in the daNGO group, indicating that the neuroprotective effects of graphene resulted from anti-inflammation. In conclusion, nano-graphene oxide has neuroprotective effects against the neurotoxin induced by 6-OHDA on dopaminergic neurons.