2005
DOI: 10.1002/jnr.20599
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Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase‐2 via CD40: Relevance to Parkinson's disease

Abstract: A glial reaction associated with up-regulation of inflammatory molecules has been suggested to play an important role in dopaminergic neuron loss in Parkinson's disease (PD). Among inflammatory molecules, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been focused upon as key factors in the pathogenesis. However, the mechanism of how these molecules are induced in PD brains is not clearly understood. We focused on CD 40, which is expressed on neural cells and could be implicated in th… Show more

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Cited by 50 publications
(34 citation statements)
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“…Third, IFN-␥ levels have also been shown to be increased in CSF and in the substantia nigra of PD patients (Widner et al, 2002). Fourth, IFN-␥ has been shown to upregulate iNOS, by binding the IFN-␥ receptor and by upregulating expression of astrocyte CD23 (Okuno et al, 2005). Interestingly, CD23 is found in glia from the SNc of PD patients, yet it is not detected in control subjects (Hunot et al, 1999).…”
Section: Discussionmentioning
confidence: 99%
“…Third, IFN-␥ levels have also been shown to be increased in CSF and in the substantia nigra of PD patients (Widner et al, 2002). Fourth, IFN-␥ has been shown to upregulate iNOS, by binding the IFN-␥ receptor and by upregulating expression of astrocyte CD23 (Okuno et al, 2005). Interestingly, CD23 is found in glia from the SNc of PD patients, yet it is not detected in control subjects (Hunot et al, 1999).…”
Section: Discussionmentioning
confidence: 99%
“…Primary microglia were prepared as described (8,25). Mixed cells prepared from cerebrums of newborn mice were cultured in media (10% FBS-DMEM) for 14 d. Next, microglia were detached by shaking, and the detached cells were replated onto a noncoated dish.…”
Section: Cell Cultures and Immunocytochemistrymentioning
confidence: 99%
“…To investigate the involvement of Sema4D in activation of microglia, we first examined the effects of Sema4D on the production of iNOS, one of the effector molecules in neuroinflammation (8,27). Although iNOS production by a microglial cell line 6-3 cells or primary microglia was not detected upon incubation with recombinant Sema4D or control IgG alone (Fig.…”
Section: Sema4d Enhances Inos and No Production In Microgliamentioning
confidence: 99%
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“…It is also believed that reactive nitrogen species (RNS), such as nitric oxide (NO) and peroxynitrite, play a major role in the toxicity of nigrostriatal dopaminergic neurons in PD (15,16). NO is synthesised from L-arginine by the enzymes nitric oxide synthases (NOS) (17).…”
Section: Experimental Designmentioning
confidence: 99%