Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Kohutnicka, M; Lewandowska, Eliza; Kurkowska‐Jastrzębska, Iwona; Członkowski, Andrzej; Członkowska, Anna

doi:10.1016/s0162-3109(98)00022-8

Cited by 260 publications

(191 citation statements)

References 40 publications

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“…This study demonstrated that MHC II also co‐localized with the astrocytic marker GFAP, as previously shown (Kurkowska‐Jastrzebska et al, 1999a; Wong et al, 1984), suggesting that the increase in MHC II levels may arise from astrocytes. The increase in MHC II protein levels seen coincides with increased GFAP expression after MPTP treatment (Kohutnicka et al, 1998) adding further support to astrocytes potentially being the predominant source of the MHC II upregulation. In the striatum MHC II levels were not elevated until 14 days after MPTP treatment which is consistent with previous work (Kurkowska‐Jastrzebska et al, 1999b).…”

Section: Discussionmentioning

confidence: 87%

“…Administration of MPTP results in reactive gliosis beginning one day after MPTP treatment for microglia and two days after MPTP for astrocytes (Kohutnicka et al, 1998). To see if the degree of reactive gliosis was altered in MHC II null mice, the number of Iba1‐positive microglia and the number of GFAP‐positive astrocytes were stereologically counted one and two days after MPTP treatment respectively.…”

Section: Resultsmentioning

confidence: 99%

“…This may be a lack of infiltrating T‐cells and IFNγ release, as IFNγ in combination with TNFα is an important activator of astrocytes (Dong and Benveniste, 2001). Activated microglia can increase astrocyte number in vitro (Rohl et al, 2007) and the astrogliosis seen in PD/MPTP has an astrogenic component (Kohutnicka et al, 1998). Taken together this suggests that the attenuation of astrogliosis in MHC II null mice was just a downstream effect of reduced microgliosis.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for a role of adaptive immune response in the disease pathogenesis of theMPTPmouse model of Parkinson's disease

Martin

Santoro

Mustafa

et al. 2015

Glia

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Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major histocompatibility complex II (MHC II) reactive cells have long been recognised in the brains of PD patients at post‐mortem. However whether cells expressing MHC II play an active role in PD pathogenesis has not been delineated. This was addressed utilising a transgenic mouse null for MHC II and the parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In wild‐type mice MHC II levels in the ventral midbrain were upregulated 1–2 days after MPTP treatment and MHC II was localized in both astrocytes and microglia. MHC II null mice showed significant reductions in MPTP‐induced dopaminergic neuron loss and a significantly reduced invasion of astrocytes and microglia in MHC II null mice receiving MPTP compared with controls. In addition, MHC II null mice failed to show increases in interferon‐γ or tumour necrosis factor‐α in the brain after MPTP treatment, as was found in wild‐type mice. However, interleukin‐1β was significantly increased in both wild‐type and MHC II null mice. These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II‐mediated T cell activation is required for the full expression of pathology in this model of PD. GLIA 2016;64:386–395

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evidence for a role of adaptive immune response in the disease pathogenesis of theMPTPmouse model of Parkinson's disease

Martin

Santoro

Mustafa

et al. 2015

Glia

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“…In fact, NE affects the microglial release of specific cytokines [23, 24] and it has been shown that these compounds modulate the viability of mesencephalic neurons [184]. …”

Section: The Role Of Ne On Methamphetamine-induced Dopaminergic Toxicitymentioning

confidence: 99%

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Ferrucci

Giorgi

Bartalucci

et al. 2013

Current Neuropharmacology

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The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.

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“…These pathological events underlie progressive dopaminergic neuronal loss and microglial activation [5][6][7]. Indeed, neuronal loss is accompanied by robust microgliosis, astrocytosis, and release of proinflammatory neurotoxic mediators [8][9][10][11]. Recent works from our own laboratories have served to highlight the role of effector T cells (Teffs) and regulatory T cells (Tregs) in attenuating such neuroinflammatory response cascades [12,13].…”

Section: Introductionmentioning

confidence: 99%

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

et al. 2016

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Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson's disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

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Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Cited by 260 publications

References 40 publications

Evidence for a role of adaptive immune response in the disease pathogenesis of theMPTPmouse model of Parkinson's disease

Evidence for a role of adaptive immune response in the disease pathogenesis of theMPTPmouse model of Parkinson's disease

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

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