ABSTRACT
Research on Alzheimer's disease (AD) focuses mainly on neuronal death and synaptic impairment induced by â-Amyloid peptide (Aâ), events at least partially mediated by astrocyte and microglia activation. However, substantial white matter damage and its consequences on brain function warrant the study of oligodendrocytes participation in the pathogenesis and progression of AD. Here, we analyze reports on oligodendrocytes' compromise in AD and discuss some experimental data indicative of Aâ toxicity in culture. We observed that 1 ìM of fibrilogenic Aâ peptide damages oligodendrocytes in vitro; while pro-inflammatory molecules (1 ìg/ml LPS + 1 ng/ml IFNã) or the presence of astrocytes reduced the Ab-induced damage. This agrees with our previous results showing an astrocyte-mediated protective effect over Aâ-induced damage on hippocampal cells and modulation of the activation of microglial cells in culture. Oligodendrocytes protection by astrocytes could be, either by reduction of Aâ fibrilogenesis/deposition or prevention of oxidative damage. Likewise, the decrease of Aâ-induced damage by proinflammatory molecules could reflect the production of trophic factors by activated oligodendrocytes and/or a metabolic activation as observed during myelination. Considering the association of inflammation with neurodegenerative diseases, oligodendrocytes impairment in AD patients could potentiate cell damage under pathological conditions.
Subject(s)
Animals , Alzheimer Disease/complications , Oligodendroglia , Amyloid beta-Peptides/toxicity , Inflammation/chemically inducedABSTRACT
Brain glial cells secrete several molecules that can modulate the survival of neurons after various types of damage to the CNS. Activated microglia and astrocytes closely associate to amyloid plaques in Alzheimer Disease (AD). They could have a role in the neurotoxicity observed in AD because of the inflammatory reaction they generate. There is controversy regarding the individual part played by the different glial cells, and the interrelationships between them. Both astrocytes and microglia produce several cytokines involved in the inflammatory reaction. Moreover, the same cytokines may have different effects, depending on their concentration and the type of cells in the vicinity. In turn, the events occurring in response to injury may lead to changes in the nature and relative concentration of the various factors involved. To learn about these putative glial interrelationships, we examined some effects of astrocytes on microglial activation.