Minocycline treatment reduces COX-2 and microgial activation in response to Aβ1-42 pep tide in a rat model of Aβ toxicity

摘要

Minocycline, a semisynthetic derivative of tetracycline with anti-inflammatory properties, acts as a neuroprotective drug in a variety of neurodegenerative models. The aim of this study was to assess the effects of minocycline treatment in inflammatory mechanisms, such gliosis, COX-2, and iNOS activation, in response to injections of oligomers of Aβ1-42 peptide in the retrosplenial cortex of the rat. Control animals were injected with reversible peptide AP42-1. As expected, minocycline attenuated microglial activation as confirmed by significant decreased in the density of a 95 kDa protein band and a marked reduction of OX-42 immunoreactivity. Our results also show that minocycline significantly reduced COX-2 protein level in Aβ-injected rat brain. Our present data, however, show that minocycline failed to mitigate either astrocytic response or iNOS activity. These results indicate the effectiveness of minocycline in modulating microglial activation and COX-2 activity, which could contribute to neuroprotection in response to the neurotoxicity induced by Aβ1-42 peptide, and also support its controversy mixed results.