Interleukin (IL)-1β, IL-2, IL-4, IL-6 and transforming growth factor-α levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease

Mogi, Makio; Harada, Minoru; Narabayashi, Hirotaro; Inagaki, Hirofumi; Minami, Masayasu; Nagatsu, Toshiharu

doi:10.1016/0304-3940(96)12706-3

Cited by 516 publications

(348 citation statements)

References 25 publications

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“…In the substantia nigra (SN) of PD patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD, key enzymes involved in reactive oxygen species (ROS) production, such as microglial NAPDH oxidase, are upregulated in damaged areas and contribute to DA neuronal death (4)(5)(6)(7). In addition, proinflammatory cytokines, such as IL-1b and TNF-a, are augmented in PD patients (8,9) and participate in DA neuronal death in the MPTP model of PD (10,11).…”

Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

111

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

111

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“…[12][13][14][15] Moreover, TNF-a concentrations are higher than normal in multiple sclerosis (MS) patients 16 and in Alzheimer's patients, 17 while TNF-a and IL-1b levels are increased in those afflicted by Parkinson's disease. 18 Moreover, TNF-a KO mice are protected against neuronal death in models of Parkinson's disease. 19 It has also been demonstrated that TNF-a mRNA synthesis is increased during ischemia and that microglia were the source of the cytokine production.…”

Section: Innate Immunity and The Central Nervous Systemmentioning

confidence: 99%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the b-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

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“…Although the mechanism by which these neurons degenerate is still unknown, it is known that inflammation has an important role in the pathogenesis of PD (McGeer et al, 1988;Hunot and Hirsch, 2003). In PD, interleukin (IL)-1␤ expression is increased in the striatum (Mogi et al, 1994), CSF (Mogi et al, 1996), and mononuclear cells in the peripheral blood (Bessler et al, 1999). Elevation of IL-1␤ expression has been used as a sensitive and specific marker of caspase-1 activation, because caspase-1 is the primary activator of pro-IL-1␤.…”

Section: Introductionmentioning

confidence: 99%

Caspase-11 Mediates Inflammatory Dopaminergic Cell Death in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease

Furuya¹,

Hayakawa²,

Yamada³

et al. 2004

J. Neurosci.

132

108

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The present study was designed to elucidate the inflammatory and apoptotic mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a model of Parkinson's disease. Our results showed that mutant mice lacking the caspase-11 gene were significantly more resistant to the effects of acute treatment with MPTP than their wild-type mice. Thus, the neurotoxicity of MPTP seems to be mediated by the induction of both mitochondrial dysfunction and free radical generation. Previously, we showed that overexpression of the Apaf-1 dominant-negative inhibitor inhibited the mitochondrial apoptotic cascade in chronic MPTP treatment but not in acute MPTP treatment. The present results indicate that MPTP neurotoxicity may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade.

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Interleukin (IL)-1β, IL-2, IL-4, IL-6 and transforming growth factor-α levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease

Cited by 516 publications

References 25 publications

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Caspase-11 Mediates Inflammatory Dopaminergic Cell Death in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease

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