Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease

Vijitruth, Rattanavijit; Liu, Mei; Choi, Dong‐Young; Nguyen, Xuan V.; Hunter, Randy L.; Bing, Guoying

doi:10.1186/1742-2094-3-6

Cited by 206 publications

(67 citation statements)

References 52 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammatory type microglia are considered detrimental to neuron survival after a neuro-toxin insult [36] and blockade of microglia activation was neuroprotective in the MPTP mouse model of PD [24], [37], [38], [39], [40], [41], [42].…”

Section: Resultsmentioning

confidence: 99%

BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

et al. 2011

View full text Add to dashboard Cite

There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions.

show abstract

Section: Resultsmentioning

confidence: 99%

BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

et al. 2011

View full text Add to dashboard Cite

show abstract

“…31,32) COX-2 is being strongly considered to play a crucial role in the neurodegenerative processes and in the intense inflammatory responses followed by neuronal death eventually in an over-threshold condition to cells. 33,34) Indeed, the suppression of COX-2 alone or both COX-1 and COX-2 by selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in neural injury models has been observed to exert a neuroprotective effect. [35][36][37][38] A previous study showed that CR, which contains TCA as a main component, suppresses COX-2 expression in the LPS-stimulated RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Pyo

Jeong

Yeo

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The anti-inflammatory and neuroprotective effects of trans-cinnamaldehyde (TCA) were investigated on the inflammatory cells and the dopaminergic degeneration in mice. TCA inhibited the up-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-induced inflammatory BV2 microglial cells. To investigate the TCA efficacy on the 6-hydroxydopamine (6-OHDA)-induced dopaminergic degeneration in mice, an intracerebroventricular injection of 6-OHDA was given to the mice, and TCA (30 mg/kg) was intraperitoneally administered. At 7 d after the 6-OHDA injection, 6-OHDA led to a severe loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the striatum and substantia nigra (SN). On the other hand, TCA dramatically maintained the number of TH-positive dopaminergic neurons in the striatum and SN regions of the 6-OHDA-treated mice, which indicates that TCA is able to inhibit the 6-OHDA-induced reduction of TH expression in the dopaminergic neurons in the striatum and SN regions. TCA also inhibited the induction of iNOS and COX-2 in the 6-OHDA model, similarly as shown in the LPS-induced inflammatory BV2 microglial cells. These results indicate that TCA has a neuroprotective effect on dopaminergic neurons and that this effect may be associated with the inhibition of inflammatory responses. These findings suggest that TCA may be a therapeutic candidate for the prevention of inflammationmediated neurodegenerative diseases.

show abstract

“…Several other endogenous peptides and environmental triggers such as paraquat [20], substance P [21], maneb [22], diesel exhaust particles [16] and rotenone [23] also directly activate microglia to cause neurotoxicity. Further, inflammation is also a noted contributor to direct neuron damage, as MPTP toxicity is significantly reduced in mutant mice deficient in pro-inflammatory factors, such as superoxide [24,25], myeloperoxidase [26], prostaglandins [27][28][29][30], NO (nitric oxide) [31] and TNFα [32][33][34].…”

Section: Microglia and Da Neuron Damagementioning

confidence: 99%

Chronic microglial activation and progressive dopaminergic neurotoxicity

Block

Hong

2007

Biochemical Society Transactions

283

223

View full text Add to dashboard Cite

PD (Parkinson's disease) is characterized by the selective and progressive loss of DA neurons (dopaminergic neurons) in the substantia nigra. Inflammation and activation of microglia, the resident innate immune cell in the brain, have been strongly linked to neurodegenerative diseases, such as PD. Microglia can respond to immunological stimuli and neuronal death to produce a host of toxic factors, including cytokines and ROS (reactive oxygen species). Microglia can also become persistently activated after a single stimulus and maintain the elevated production of both cytokines and ROS, long after the instigating stimulus is gone. Current reports suggest that this chronic microglial activation may be fuelled by either dying/damaged neurons or autocrine and paracrine signals from local glial cells, such as cytokines. Here, we review proposed mechanisms responsible for chronic neuroinflammation and explain the interconnected relationship between deleterious microglial activation, DA neuron damage and neurodegenerative disease.

show abstract

Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease

Cited by 206 publications

References 52 publications

BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

BCG Vaccine-Induced Neuroprotection in a Mouse Model of Parkinson's Disease

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Chronic microglial activation and progressive dopaminergic neurotoxicity

Contact Info

Product

Resources

About