Dopaminergic neuronal death in the substantia nigra associates with change in serum levels of TNF-α and IL-1β; evidence from early experimental model of Parkinson’s disease

Piri, Hossein; Sharifi, Sahar; Nigjeh, Sepideh; Haghdoost-Yazdi, Hashem

doi:10.1080/01616412.2021.2024726

Cited by 7 publications

(2 citation statements)

References 52 publications

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“… 9 , 10 The rapid microglia activation after injection of 6-OHDA also indicates the critical role of inflammation in neurotoxin induced PD models. 11 …”

Section: Introductionmentioning

confidence: 99%

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling

Xu,

Chen,

Chen

et al. 2024

Nutr Metab Insights

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6-Hydroxydopamine (6-OHDA) is a classic neurotoxin that has been widely used in Parkinson’s disease research. 6-OHDA can increase intracellular reactive oxygen species (ROS) and can cause cell damage, which can be attenuated with (-)-Epigallocatechin-3-gallate (EGCG) treatment. However, the mechanism by which EGCG alters the 6-OHDA toxicity remains unclear; In this study, we found 6-OHDA (25 μM) alone increased intracellular ROS concentration in N27 cells, which was attenuated by pretreating with EGCG (100 μM). We evaluated the intracellular oxidative damage by determining the level of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content. 6-OHDA significantly increased TBARS by 82.7% ( P < .05) and protein carbonyl content by 47.8 ( P < .05), compared to the control. Pretreatment of EGCG decreased TBARS and protein carbonyls by 36.4% ( P < .001) and 27.7% ( P < .05), respectively, compared to 6-OHDA alone treatment. Antioxidant effect was tested with E2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and peroxisome-proliferator activator receptor γ (PPARγ) expression. 6-OHDA increased Nrf2 expression by 69.6% ( P < .001), HO-1 by 173.3% ( P < .001), and PPARγ by 122.7% ( P < .001), compared with untreatment. EGCG pretreatment stabilized these alterations induced by 6-OHDA. Our results suggested that the neurotoxicity of 6-OHDA in N27 cells was associated with ROS pathway, whereas pretreatment of EGCG suppressed the ROS generation and deactivated the Nrf2/HO-1 and PPARγ expression.

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“… 9 , 10 The rapid microglia activation after injection of 6-OHDA also indicates the critical role of inflammation in neurotoxin induced PD models. 11 …”

Section: Introductionmentioning

confidence: 99%

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling

Xu,

Chen,

Chen

et al. 2024

Nutr Metab Insights

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“…An analysis of myeloid compartment in PD patients revealed migration of peripheral monocytes to the CNS that was in sync with rodent studies (Grozdanov et al 2014 ; Harms et al 2018 ). Dopaminergic neurons in SN is highly sensitive to pro-inflammatory cytokines like TNF-α and IFNγ in models of PD (Block et al 2007 ; Piri et al 2022 ; Tansey and Goldberg 2010 ). Growing evidence also suggests a role of perturbed peripheral immune components and chronic inflammatory cascades in the pathophysiology of PD (Kannarkat et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Peripheral MC1R Activation Modulates Immune Responses and is Neuroprotective in a Mouse Model of Parkinson’s Disease

Srivastava,

Nishiyama,

Zhou

et al. 2023

J Neuroimmune Pharmacol

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Background Melanocortin 1 receptor (MC1R) is a key pigmentation gene, and loss-of-function of MC1R variants that produce red hair may be associated with Parkinson’s disease (PD). We previously reported compromised dopaminergic neuron survival in Mc1r mutant mice and dopaminergic neuroprotective effects of local injection of a MC1R agonist to the brain or a systemically administered MC1R agonist with appreciable central nervous system (CNS) permeability. Beyond melanocytes and dopaminergic neurons, MC1R is expressed in other peripheral tissues and cell types, including immune cells. The present study investigates the impact of NDP-MSH, a synthetic melanocortin receptor (MCR) agonist that does not cross BBB, on the immune system and the nigrostriatal dopaminergic system in mouse model of PD. Methods C57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed. Peripheral and CNS immune cells were phenotyped and inflammatory markers were measured. The nigrostriatal dopaminergic system was assessed behaviorally, chemically, immunologically, and pathologically. To understand the role of regulatory T cells (Tregs) in this model, CD25 monoclonal antibody was used to deplete CD25 + Tregs. Results Systemic NDP-MSH administration significantly attenuated striatal dopamine depletion and nigral dopaminergic neuron loss induced by MPTP + LPS. It improved the behavioral outcomes in the pole test. Mc1r mutant mice injected with NDP-MSH in the MPTP and LPS paradigm showed no changes in striatal dopamine levels suggesting that the NDP-MSH acts through the MC1R pathway. Although no NDP-MSH was detected in the brain, peripheral, NDP-MSH attenuated neuroinflammation as observed by diminished microglial activation in the nigral region, along with reduced TNF-α and IL1β levels in the ventral midbrain. Depletion of Tregs was associated with diminished neuroprotective effects of NDP-MSH. Conclusions Our study demonstrates that peripherally acting NDP-MSH confers protection on dopaminergic nigrostriatal neurons and reduces hyperactivated microglia. NDP-MSH modulates peripheral immune responses, and Tregs may be involved in the neuroprotective effect of NDP-MSH.

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Neuroprotective effects of fermented tea in MPTP-induced Parkinson's disease mouse model via MAPK signaling-mediated regulation of inflammation and antioxidant activity

Lee

Moon²,

Shim³

et al. 2023

Food Research International

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Dopaminergic neuronal death in the substantia nigra associates with change in serum levels of TNF-α and IL-1β; evidence from early experimental model of Parkinson’s disease

Cited by 7 publications

References 52 publications

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling

Peripheral MC1R Activation Modulates Immune Responses and is Neuroprotective in a Mouse Model of Parkinson’s Disease

Neuroprotective effects of fermented tea in MPTP-induced Parkinson's disease mouse model via MAPK signaling-mediated regulation of inflammation and antioxidant activity

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