The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease

Mirza, Bilal; Hadberg, Hanne; Thomsen, P; Moos, Torben

doi:10.1016/s0306-4522(99)00455-8

Cited by 300 publications

(200 citation statements)

References 50 publications

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“…Several studies point to a role of activated glia and inflammation in the pathogenesis of neurodegenerative diseases, especially in PD (Hirsch et al, 2005;Liu et al, 2003;Mena et al, 2002;Mirza et al, 2000). Activation of both, microglia and astroglia is seen in animal models of PD and they are considered active participants in the nigrostriatal degeneration (Halliday and Stevens, 2011;Mena and Garcia de, 2008;Teismann and Schulz, 2004;Wu et al, 2002).…”

Section: Midbrain Astroglia Responsesmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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Section: Midbrain Astroglia Responsesmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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“…Characteristic pathological features of the PD brain are a selective and progressive loss of dopamine neurons of the substantia nigra (SN) and focal accumulation of activated microglia in the SN (McGeer et al, 1988;Forno, 1996;Banati et al, 1998;Knott et al, 2000;Mirza et al, 2000). Activation of microglia also has been identified in the SN and/or striatum of the parkinsonian animal models, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian brain (O'Callaghan et al, 1990;Francis et al, 1995;Czlonkowska et al, 1996;Kohutnicka et al, 1998;Kurkowska-Jastrzebska et al, 1999) or medial forebrain bundle (MFB), which transmits axons from the nigral dopamine neurons to the striatum, axotomized rat brain (Brecknell et al, 1995;Revuelta et al, 1999;Sugama et al, 2003).…”

Section: Pathological Dynamics Of Activated Microglia In Pathogenesismentioning

confidence: 99%

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Kim

Joh²

2006

Exp Mol Med

583

450

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Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1β, TNF-α, IL-6), NO, PGE2, and superoxide. Moreover, our recent study demonstrated that activated microglia phagocytose not only damaged cell debris but also neighboring intact cells. It further supports their active participation in self-perpetuating neuronal damaging cycles. In the following review, we discuss microglial responses to damaging neurons, known activators released from injured neurons and how microglia cause neuronal degeneration. In the last part, microglial activation and their role in PD are discussed in depth.

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“…This limited astroglial environment might be a susceptibility factor for dopaminergic cells in the SN. In many but not all cases of PD and animals models of PD, a mild increase in the number of astrocytes and GFAP expression has been observed, with a more pronounced expression in experimental models (182,(185)(186)(187).…”

Section: Astrocytesmentioning

confidence: 99%

“…Aqp4-null astrocytes migrate much slower than WT astrocytes in vitro (333) and in vivo (457), and glial scarring is reduced in Aqp4 -/- (333) indicating that AQP4 may inhibit survival of injured dopaminergic neurons by scar formation. However, evidence for changes in the number or astrocyte reactivity in postmortem brains of PD patients is inconsistent (185,187), and gliosis has been shown to be more prominent in models of PD than in patients (186). Notably, upregulation of AQP4 is not necessarily co-localized with GFAP expression, as shown in a mouse model of ALS (348), and GFAP upregulation is not automatically accompanied by an increase in AQP4, evident in a model of cerebral malaria (341).…”

Section: Selective Vulnerability Mediated By the Glial Microenvironmementioning

confidence: 99%

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

et al. 2011

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The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease

Cited by 300 publications

References 50 publications

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

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