Loss of peroxisomal function from all neural cells but not from astrocytes or neurons causes axonal degeneration and dysmyelination.

摘要

It is clearly established that peroxisomes in neural cells are indispensible for the normal functioning of the postnatal brain. Nestin-Pex5 knockout mice, a model which lacks functional peroxisomes in all neural cells, show metabolic disturbances, accompanied by severe dys/demyelination, axonal degeneration, lipid accumulations and gliosis. These alterations cause motoric and cognitive decline and early death of the mice. The oligodendrocyte specific CNPase-Pex5 knockout model shows a similar but slower progressive pathology. We now report that the neuron-specific NEX-Pex5 knockout model does not show any metabolic or histological abnormality. Inactivation of peroxisomes in astrocytes, realized in the GFAP-Pex5 knockout model, leads to an accumulation of very long chain fatty acids (VLCFA) and a reduction of plasmalogens, demonstrating that peroxisomes in astrocytes do metabolize lipids. However these metabolic changes in the GFAP-Pex5 mice do not cause any adverse effect.