Mechanistic comparison between MPTP and rotenone neurotoxicity in mice

Bhurtel, Sunil,Katila, Nikita,Srivastav, Sunil,Neupane, Sabita,Choi, Dong-Young Elsevier BV 2019 NeuroToxicology Vol.71 No.-

<P><B>Abstract</B></P> <P>Animal models for Parkinson’s disease (PD) are very useful in understanding the pathogenesis of PD and screening for new therapeutic approaches. 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and rotenone are common neurotoxins used for the development of experimental PD models, and both inhibit complex I of mitochondria; this is thought to be an instrumental mechanism for dopaminergic neurodegeneration in PD. In this study, we treated mice with MPTP (30 mg/kg/day) or rotenone (2.5 mg/kg/day) for 1 week and compared the neurotoxic effects of these toxins. MPTP clearly produced dopaminergic lesions in both the substantia nigra and the striatum as shown by loss of dopaminergic neurons, depletion of striatal dopamine, activation of glial cells in the nigrostriatal pathway and behavioral impairment. In contrast, rotenone treatment did not show any significant neuronal injury in the nigrostriatal pathway, but it caused neurodegeneration and glial activation only in the hippocampus. MPTP showed no such deleterious effects in the hippocampus suggesting the higher susceptibility of the hippocampus to rotenone than to MPTP. Interestingly, rotenone caused upregulation of the neurotrophic factors and their downstream PI3K-Akt pathway along with adenosine monophosphate-activated protein kinase (AMPK) activation. These results suggest that MPTP-induced dopaminergic neurotoxicity is more acute and specific in comparison to rotenone toxicity, and compensatory brain-derived neurotrophic factor (BDNF) induction and AMPK activation in the rotenone-treated brain might suppress the neuronal injury.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Neurotoxic property of MPTP and rotenone was compared. </LI> <LI> Neurotoxicity of MPTP was acute and selective to the dopaminergic neurons. </LI> <LI> Rotenone caused glial activation and neuronal loss in the hippocampus. </LI> </UL> </P>

Strength and Durability of Bottom Ash and Lime Stabilized Bangkok Clay

Akanksha Bhurtel,Amin Eisazadeh 대한토목학회 2020 KSCE Journal of Civil Engineering Vol.24 No.2

High rainfall is observed in a tropical climatic country like Thailand that results in higher chances of natural calamities like flood. High plastic clay known as Bangkok clay is present in Thailand. The clay is famous for displaying variability in its geotechnical properties under dry and wet conditions. Therefore, such clay must be treated with some other materials for the stability of roads along with vehicles running through them. Bottom ash that is one of the waste materials produced from coal combustion has been used for this study along with lime. Tests like unconfined compressive strength test, durability test has been conducted by determining the strength under dry and wet condition. Two methods of soaking have been adopted when performing wetting-drying namely complete and capillary soaking. The results showed improvement in strength as well as durability after replacement with bottom ash and lime. The strength of the soil specimen after treatment with bottom ash and lime has improved 2-fold with 50% amount of bottom ash and 12% lime. The same ratio of materials: 50% bottom ash and lime with the clay showed the optimum amount in terms of durability.

Service Users’ Confidence in Accessing Public Services in Nepal: What Makes Differences?

Anil Kumar Gupta,Anup Bhurtel,Prakash C. Bhattarai 서울대학교행정대학원 2023 The Korean Journal of Policy Studies Vol.38 No.1

This paper presents the factors associated with service users’ confidence in receiving public services in Nepal. The factors were taken from National Governance Survey 2017/ 18 (N=7334). The survey respondents were randomly selected from 43 of 77 districts of Nepal by using four-stage multiple cluster sampling from the service users who received public services in a year duration. The result showed that service users’ confidence in receiving public services differs by their locale, education level, caste/ethnicity, not having close contact (Afno Manchhe), and presence of intermediaries. Education, not having a person in close contact (Afno manchhe) and the presence of intermediaries have a negative effect, whereas locale (rural) and caste/ethnicity (Brahman/Chettri) have positive effects on service users’ confidence in accessing public services. Consideration of these factors boosts the confidence of the service users, which, in turn, promotes effective service delivery.

Enhanced neuroinflammatory responses after systemic LPS injection in IL-32β transgenic mice

Neupane, Sabita,Srivastav, Sunil,Bhurtel, Sunil,Katila, Nikita,Shadfar, Sina,Park, Pil-Hoon,Hong, Jin Tae,Choi, Dong-Young Elsevier 2018 Journal of chemical neuroanatomy Vol.94 No.-

<P><B>Abstract</B></P> <P>IL-32 is a proinflammatory cytokine, and involved in various diseases including infection, inflammation, and cancer. However, effects of IL-32 on neuroinflammation remain obscure. Herein, we examined the effects of IL-32β on systemic LPS-induced neuroinflammation using IL-32β transgenic (Tg) mice. IL-32β wild type (WT) and Tg mice received LPS injection (5 mg/kg, i.p.), and then neuroinflammatory responses were evaluated. Systemic LPS caused remarkable gliosis in the brain at 12 h regardless of genotypes. The gliosis in WT mice was sustained by 24 h, whereas it became more severe in Tg mice by 24 h. Proinflammatory cytokines and proteins were increased at 12 h both in WT and Tg brains. The elevated levels of TNFα and VCAM-1were not altered over time, while levels of IL-6, IL-1β and iNOS were dropped in WT mice. In contrast, elevated levels IL-6, IL-1β, iNOS and VCAM-1 were sustained, and level of TNFα was augmented in Tg brains by 24 h. Interestingly, level of IL-10 mRNA in Tg mice was remarkably higher than in WT mice at 0 h, which was decreased at 12 h and maintained by 24 h. In WT brain, mRNA level of IL-10 was raised at 12 h after LPS injection, and further increased at 24 h. Activation of NF-κB signaling pathway was detected in glia cells after LPS injection which was exaggerated at 24 h in Tg mice in comparison to WT mice. These results indicate that IL-32β enhances neuroinflammatory responses caused by systemic LPS, and this might be attributable to prolonged activation of NF-κB signaling pathway.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Effects of IL-32β on neuroinflammation were evaluated. </LI> <LI> Enhanced neuroinflammation was observed in IL-32β transgenic mice. </LI> <LI> Prolonged activation of NF-κB might be related to extended neuroinflammation. </LI> </UL> </P>

Neuroprotective Effects of Antidepressants via Upregulation of Neurotrophic Factors in the MPTP Model of Parkinson’s Disease

Shadfar, S.,Kim, Y. G.,Katila, N.,Neupane, S.,Ojha, U.,Bhurtel, S.,Srivastav, S.,Jeong, G. S.,Park, P. H.,Hong, J. T. HUMANA PRESS INC 2018 Molecular Neurobiology Vol.55 No.1

<P>Neurotrophic factors are essential for neuronal survival, plasticity, and development and have been implicated in the action mechanism of antidepressants. In this study, we assessed the neurotrophic factor-inducing and neuroprotective properties of antidepressants. In the first part of the study, we found that fluoxetine, imipramine, and milnacipran (i.p., 20 mg/kg/day for 1 week or 3 weeks) upregulated brain-derived neurotrophic factor in the striatum and substantia nigra both at 1 week and 3 weeks. In contrast, an increase in the glial-derived neurotrophic factor was more obvious at 3 weeks after the antidepressants treatment. Specifically, it was found that fluoxetine and imipramine are more potent in raising the levels of neurotrophic factors than milnacipran. Furthermore, antidepressants elevated the phosphorylation of extracellular signal-regulated-protein kinase (ERK1/2) and the serine/threonine kinase Akt. In the second part of the study, we compared the neuroprotective effects of fluoxetine, imipramine, and milnacipran in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Pretreament with fluoxetine, imipramine or milnacipran for 3 weeks reduced MPTP-induced dopaminergic neurodegeneration and microglial activation in the nigrostriatal pathway. Neurochemical analysis by HPLC exhibited that antidepressants attenuated the depletion of striatal dopamine. In consistent, beam test showed that behavioral impairment was ameliorated by antidepressants. Neuroprotective effects were more prominent in the fluoxetine or imipramine treatment group than in milnacipran treatment group. Finally, we found that neuroprotection of the antidepressants against 1-methyl-4-phenylpyridinium neurotoxicity in SH-SY5Y cells was attenuated by ERK or Akt inhibitor. These results indicate that neuroprotection by antidepressants might be associated with the induction of neurotrophic factors, and antidepressant could be a potential therapeutic intervention for treatment of Parkinson's disease.</P>