Interferon-γ Involvement in the Neuroinflammation Associated with Parkinson’s Disease and L-DOPA-Induced Dyskinesia

Ferrari, Daniele Pereira; Bortolanza, Mariza; Del‐Bel, Elaine

doi:10.1007/s12640-021-00345-x

Cited by 16 publications

(12 citation statements)

References 74 publications

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“…Differences in survival time after MPTP and methodological approaches could account for the different results obtained in the MPTP + L-Dopa monkeys between these studies. Several preclinical studies in rodent models of PD have shown that treatment with L-Dopa induces or exacerbates inflammation via a direct involvement of microglia releasing pro-inflammatory cytokines promoting an initiation and/or development of dyskinesias [ 72 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. In fact, the strong positive correlations between Iba1 levels and dyskinetic scores measured in several basal ganglion nuclei in the present study strongly support a direct link between LID and microglial reactivity.…”

Section: Discussionmentioning

confidence: 99%

Prevention of L-Dopa-Induced Dyskinesias by MPEP Blockade of Metabotropic Glutamate Receptor 5 Is Associated with Reduced Inflammation in the Brain of Parkinsonian Monkeys

Morissette

Bourque

Tremblay

et al. 2022

Cells

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Proinflammatory markers were found in brains of Parkinson’s disease (PD) patients. After years of L-Dopa symptomatic treatment, most PD patients develop dyskinesias. The relationship between inflammation and L-Dopa-induced dyskinesias (LID) is still unclear. We previously reported that MPEP (a metabotropic glutamate receptor 5 antagonist) reduced the development of LID in de novo MPTP-lesioned monkeys. We thus investigated if MPEP reduced the brain inflammatory response in these MPTP-lesioned monkeys and the relationship to LID. The panmacrophage/microglia marker Iba1, the phagocytosis-related receptor CD68, and the astroglial protein GFAP were measured by Western blots. The L-Dopa-treated dyskinetic MPTP monkeys had increased Iba1 content in the putamen, substantia nigra, and globus pallidus, which was prevented by MPEP cotreatment; similar findings were observed for CD68 contents in the putamen and globus pallidus. There was a strong positive correlation between dyskinesia scores and microglial markers in these regions. GFAP contents were elevated in MPTP + L-Dopa-treated monkeys among these brain regions and prevented by MPEP in the putamen and subthalamic nucleus. In conclusion, these results showed increased inflammatory markers in the basal ganglia associated with LID and revealed that MPEP inhibition of glutamate activity reduced LID and levels of inflammatory markers.

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Section: Discussionmentioning

confidence: 99%

Prevention of L-Dopa-Induced Dyskinesias by MPEP Blockade of Metabotropic Glutamate Receptor 5 Is Associated with Reduced Inflammation in the Brain of Parkinsonian Monkeys

Morissette

Bourque

Tremblay

et al. 2022

Cells

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“…For example, IL-1β is a driver of multiple sclerosis (MS), and mice deficient in IL-1β are resistant to experimental autoimmune encephalomyelitis (EAE) ( 41 ). TNF-α secreted by glial cells generally perpetuates neuroinflammation ( 42 ), and IFN-γ activates glial cells and is increased in Parkinson’s disease ( 43 ). Finally, IL-6, a pleiotropic cytokine, has several roles that can be both neuroprotective or neuroinflammatory ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages

Wallace

Gonzalez

Rajan

et al. 2022

Antimicrob Agents Chemother

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“…A high CD4+/CD8+ characterizes PD 60 . IFN-γ induces loss of dopamine neurons and nigrostriatal degeneration 61 .…”

Section: Tgf and Ifnmentioning

confidence: 99%

Long Covid and Neurodegenerative Disease

Chambers¹

2023

Preprint

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Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased TGF beta/IFN gamma with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4+ and CD8+ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF beta/IFN gamma and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

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Interferon-γ Involvement in the Neuroinflammation Associated with Parkinson’s Disease and L-DOPA-Induced Dyskinesia

Cited by 16 publications

References 74 publications

Prevention of L-Dopa-Induced Dyskinesias by MPEP Blockade of Metabotropic Glutamate Receptor 5 Is Associated with Reduced Inflammation in the Brain of Parkinsonian Monkeys

Prevention of L-Dopa-Induced Dyskinesias by MPEP Blockade of Metabotropic Glutamate Receptor 5 Is Associated with Reduced Inflammation in the Brain of Parkinsonian Monkeys

Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages

Long Covid and Neurodegenerative Disease

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