Relationship of Complement-Activated Oligodendrocytes to Reactive Microglia and Neuronal Pathology in Neurodegenerative Disease

Yamada, Takashi; McGeer, Patrick L.; McGeer, E.G.

doi:10.1159/000107179

Cited by 20 publications

(18 citation statements)

References 17 publications

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“…Oligodendrocytes are vulnerable to complement attack, which is particularly observed in multiple sclerosis (Compston et al, 1988;Prineas et al, 2001;Schwab and McGeer, 2002), and this vulnerability may be related to a deficiency of their ability to express complement regulatory proteins (Scolding et al, 1998). Sporadic complement attack, in the form of complementactivated oligodendroglia (CAO), is also observed in a number of neurodegenerative conditions (Yamada et al, 1990(Yamada et al, , 1991, including Alzheimer's, Pick's, Huntington's, and Parkinson's diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, ShyDrager syndrome, argyrophilic grain dementia, and pallido-nigral luysial atrophy (Yamada et al, 1990(Yamada et al, , 1991. The source of the complement proteins that become activated is unknown, but the data presented here indicate that oligodendrocytes themselves may be one source.…”

Section: Discussionmentioning

confidence: 99%

Expression of complement messenger RNAs and proteins by human oligodendroglial cells

Hosokawa

Klegeris

Maguire

et al. 2003

Glia

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Neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing most, if not all, of the complement proteins. Little is known, however, about the capacity of oligodendroglial cells to generate complement components. This study evaluated expression of complement mRNAs and their protein products by human oligodendrocytes. Cells were isolated and cultured from white matter of seven adult cases that had undergone surgical temporal lobe resection for epilepsy. Oligodendroglial cultures were characterized by the expression of such cell type-specific mRNAs as myelin proteolipid protein (PLP), oligodendrocyte-specific protein (OSP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and were further characterized by immunostaining for such differentiation markers as myelin basic protein (MBP), PLP, CNPase, and O4. RT-PCR analysis showed that the oligodendroglial cells expressed detectable levels of complement mRNAs for the C1q B-chain, C1r, C1s, C2, C3, C4, C5, C6, C7, C8 gamma subunit, and C9. Immunostaining was positive for C1q, C1s, C2, C3, C4, C5, C6, C7, C8, and C9. Double immunostaining for the oligodendrocyte marker O4 and the complement protein C3 demonstrated that all O4-positive cells were also positive for C3, indicating constitutive C3 expression. These results indicate that oligodendroglial cells may be a source of complement proteins in human brain and thus could contribute to the pathogenesis of several neurodegenerative and inflammatory diseases of the CNS, such as Alzheimer's disease, multiple sclerosis, and progressive supranuclear palsy, where complement-activated oligodendrocytes are abundant.

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Section: Discussionmentioning

confidence: 99%

Expression of complement messenger RNAs and proteins by human oligodendroglial cells

Hosokawa

Klegeris

Maguire

et al. 2003

Glia

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“…Indeed, increased mRNA levels of complement components have been found in affected brain regions (McGeer and McGeer, 2004). The presence of complement components, including all constituents of the membrane attack complex (MAC), has been shown intracellularly on Lewy bodies and on oligodendroglia in the SN of PD patients (Yamada et al, 1991(Yamada et al, , 1992(Yamada et al, , 1993. Accumulation of Lewy bodies can apparently cause the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products such as the MAC, hydroxyl radicals, and excess glutamate (GLU) (McGeer and McGeer, 1998).…”

Section: Studymentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Esposito

Matteo

Benigno

et al. 2007

Experimental Neurology

218

176

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Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron-glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2) is upregulated in SNc DAergic neurons in both PD patients and animal models of PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine degeneration. Moreover, recent epidemiological studies have revealed that the risk of developing PD is reduced in humans who make therapeutical use of NSAIDs. Consequently, it is hypothesized that they might delay or prevent the onset of PD. However, whether or not these common drugs may also be of benefit to those individuals who already have Parkinson's disease has not as yet been shown.In this paper, evidence relating to the protective effects of aspirin or other NSAIDs on DAergic neurons in animal models of Parkinson's disease will be discussed. In addition, the pharmacological mechanisms by which these molecules can exert their neuroprotective effects will be reviewed. Finally, epidemiological data exploring the effectiveness of NSAIDs in the prevention of PD and their possible use as adjuvants in the therapy of this neurodegenerative disease will also be examined.

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“…In neurons, this type of cell death can be induced by agents such as glutamate (Nicotera et al, 1996), 6-hydroxy-dopamine (Walkinshaw and Waters, 1994), organotin (Thompson et al, 1996), as well as by traumatic or irradiation injury (Rink et al, 1995;Ferrer et al, 1995), involving different signalling pathways (Ceruti et al, 1997;Hu, Van Eldik, 1996). Whether cells undergoing apoptosis do or do not induce an inflammatory response is still a matter of debate (Vela et al, 1996;Ferrer et al, 1992Ferrer et al, , 1995Yamada et al, 1991;Mehmet and Edwards, 1996;Rink et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis by mercury compounds depends on maturation and is not associated with microglial activation

Monnet‐Tschudi

1998

J. Neurosci. Res.

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The earliest sign of neurotoxicity observed after exposure of three-dimensional brain cell cultures to low concentrations of mercury compounds is a microglial reaction. We hypothesized that an induction of apoptosis by mercury compounds could be an activating signal of the microglial reaction. Aggregating brain cell cultures of fetal rat telencephalon were treated for 10 days with either mercury chloride or monomethylmercury chloride at noncytotoxic concentrations during two developmental periods: from day 5 to 15, corresponding to an immature stage, and from day 25 to 35 corresponding to a mature stage. Apoptosis was evaluated by the TUNEL technique. It was found that both mercury compounds caused a significant increase in the number of apoptotic cells, but exclusively in immature cultures exhibiting also spontaneous apoptosis. Double staining by the TUNEL technique combined with either neuronal or astroglial markers revealed that the proportion of cells undergoing apoptosis was highest for astrocytes. Furthermore neither an association nor a colocalization was found between apoptotic cells and microglial cells. In conclusion, it appears that the induction of apoptosis by mercury compounds in immature cells is only an acceleration of a spontaneously occurring process, and that it is not a directly related to the early microglial reaction.

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Relationship of Complement-Activated Oligodendrocytes to Reactive Microglia and Neuronal Pathology in Neurodegenerative Disease

Cited by 20 publications

References 17 publications

Expression of complement messenger RNAs and proteins by human oligodendroglial cells

Expression of complement messenger RNAs and proteins by human oligodendroglial cells

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Induction of apoptosis by mercury compounds depends on maturation and is not associated with microglial activation

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