| First Author | Oeckl P | Year | 2012 |
| Journal | Neurobiol Dis | Volume | 48 |
| Issue | 3 | Pages | 481-7 |
| PubMed ID | 22750522 | Mgi Jnum | J:197510 |
| Mgi Id | MGI:5493208 | Doi | 10.1016/j.nbd.2012.06.010 |
| Citation | Oeckl P, et al. (2012) Astrocyte-specific IKK2 activation in mice is sufficient to induce neuroinflammation but does not increase susceptibility to MPTP. Neurobiol Dis 48(3):481-7 |
| abstractText | A key regulator of inflammatory gene expression is the transcription factor NF-kappaB that is controlled by the IkappaB proteins. We used a transgenic mouse model expressing a constitutively active IkappaB-kinase-2 (IKK2-CA) in astrocytes under control of the human glial fibrillary acidic protein promotor (IKK2-mice) to investigate neuroinflammation, proinflammatory cytokine expression, microglial activation and a potential enhanced susceptibility to the neurotoxin MPTP (4x10 mg/kg). Readouts included the determination of cytokines, striatal dopamine (DA), nigral tyrosine hydroxylase (TH) positive neurons, microglial activation and motor activity. IKK2-CA expression in astrocytes conditionally induced by the tet-off system resulted in a widespread neuroinflammation indicated by the increased expression of inflammatory cytokines and the presence of activated microglia and astrogliosis. Additionally, striatal DA concentrations but not nigral TH-positive neurons were reduced in IKK2-mice by 20%. Motor activity of IKK2-mice was not affected. Surprisingly, there was a similar reduction in striatal DA concentrations and the number of nigral TH-positive neurons in IKK2 and control mice after MPTP treatment. In conclusion, although naive IKK2-mice showed reduced striatal DA concentrations and an increase in inflammatory markers in the brain, a higher susceptibility to MPTP was not observed. This finding argues against a prominent role of astrocyte specific, IKK2-mediated neuroinflammation in MPTP-induced neurodegeneration. |
