Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice

Jung, Yu Yeon; Katila, Nikita; Neupane, Sabita; Shadfar, Sina; Ojha, Uttam; Bhurtel, Sunil; Srivastav, Sunil Kumar; Son, Dong Ju; Park, Pil-Hoon; Yoon, Do Young; Hong, Jin Tae; Choi, Dong‐Young

doi:10.1016/j.neuint.2016.12.002

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…Moreover, regarding the published data using the MPTP model, the selective activation of p38 MAPK upstream of NF-kB in the SNpc neurons of mice treated with MPTP has been described as one that can promote neurodegeneration processes (Karunakaran and Ravindranath, 2009 ), and TNF-α was also identified as an early upstream activator of the ASK1-MAPK death signaling pathway after MPTP intoxication (Ray et al, 2015 ). IL-32b exaggerated the MPTP-mediated activation of p38 MAPK and JNK pathways, which have been shown to be involved in MPTP neurotoxicity (Jung et al, 2017 ). In fact, a new hypothesis for PD pathogenesis that points out the role of p38 MAPK pathway in the modulation of autophagy in cell death processes has recently been proposed (Obergasteiger et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice

Gil-Martínez

Cuenca‐Bermejo

Gallo-Soljancic

et al. 2020

Front. Aging Neurosci.

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Background: Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the pERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.

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Section: Discussionmentioning

confidence: 99%

Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice

Gil-Martínez

Cuenca‐Bermejo

Gallo-Soljancic

et al. 2020

Front. Aging Neurosci.

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“…To quantify the loss of TH‐positive neurons in the substantia nigra, six sections covering the rostral to caudal substantia nigra were selected from each brain. The number of TH‐positive cells was stereologically counted as described in a previous study . The TH‐fiber density in the striatum was determined using Image J software as described in a previous study …”

Section: Methodsmentioning

confidence: 99%

“…The number of TH-positive cells was stereologically counted as described in a previous study. 23 The TH-fiber density in the striatum was determined using Image J software as described in a previous study. 24 The extent of gliosis was evaluated as described previously.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…24 The extent of gliosis was evaluated as described previously. 23 Briefly, microscopic images of the substantia nigra pars compacta or striatum were captured, and GFAP-or Iba1-immunoreactive cells were analyzed using ImageJ software (http:// rsbweb.nih.gov/ij/). The pixel threshold was adjusted to 200 and the number of pixels above the threshold was quantified.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

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Methylene blue protects dopaminergic neurons against MPTP‐induced neurotoxicity by upregulating brain‐derived neurotrophic factor

Bhurtel

Katila

Neupane

et al. 2018

Annals of the New York Academy of Sciences

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The relatively old, yet clinically used, drug methylene blue (MB) is known to possess neuroprotective properties by reducing aggregated proteins, augmenting the antioxidant response, and enhancing mitochondrial function and survival in various models of neurodegenerative diseases. In this study, we aimed to examine the effects of MB in Parkinson's disease (PD) in vivo and in vitro models by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP ) with a focus on possible effects on induction of neurotrophic factors. Our results indicate that pretreatment with MB significantly attenuated MPTP-induced loss of dopaminergic neurons, glial cell activation, and depletion of dopamine. We also found that MB upregulated brain-derived neurotrophic factor (BDNF) and activated its downstream signaling pathways, suggesting that BDNF might be a contributor to MB-associated neuroprotection. Specific inhibition of the BDNF receptor or extracellular signal-regulated kinase (Erk) reversed the MB-mediated protection against MPP toxicity, thus implying a role for BDNF and the Erk pathway in the neuroprotective effects. Taken together, our data suggest that MB protects neurons from MPTP neurotoxicity via induction of BDNF. Further study to determine whether MB preserves dopaminergic neurons in the brains of PD patients is warranted.

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“…A newly-identified proinflammatory cytokine, interleukin (IL)-32 was found to worsening MPTP neurotoxicity by inducing neuroinflammation [17]. Another cytokines IL-4 and IL-13 have been suggested to have an effect on cognitive functions by stimulation of astrocytes and attention was drawn to the relationship with dementia due to Parkinson's disease [18].…”

Section: New Pathways and Targets Associated With Cytokines In Parkinson's Diseasementioning

confidence: 99%

Proinflammatory cytokines in Parkinson’s disease and current treatment approaches

Ahmet¹

2020

GSC Adv. Res. Rev.

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Parkinson's disease is a neurodegenerative disease characterized by progressive degeneration of dopaminergic neurons in the substantia nigra region. As the etiology is not clear, treatment in this disease is rather symptomatic and inadequate to prevent the progression of the disease. However, recent studies have demonstrated the strong association of neuroinflammation and proinflammatory cytokines with disease pathology. In this review, the relationship of proinflammatory cytokines with the pathology of Parkinson's disease is discussed and current treatment approaches targeting these mechanisms are evaluated.

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Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice

Cited by 14 publications

References 37 publications

Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice

Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice

Methylene blue protects dopaminergic neurons against MPTP‐induced neurotoxicity by upregulating brain‐derived neurotrophic factor

Proinflammatory cytokines in Parkinson’s disease and current treatment approaches

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