Influence of factors secreted by wobbler astrocytes on neuronal and motoneuronal survival

During late postnatal development, mice with the autosomal recessive wobble r mutation (wr/wr) develop motoneuron degeneration associated with astrogli osis in the spinal cord. In vitro, primary wobbler astrocytes are also affe cted, exhibiting abnormal cell-cell contacts. To characterize further the w obbler disease, we investigated the in vitro effects of wobbler astrocytes on primary neuronal cultures from the spinal cords of 15-day-old wild-type mouse and rat embryos. Cocultures with the wobbler astrocytes, or direct ad dition of wobbler astrocyte-conditioned medium, led to a decrease in neuron number in primary mixed neuronal cultures, containing motoneurons and inte rneuron-like cells. In contrast, wobbler astrocyte-conditioned medium enhan ced survival of highly purified motoneurons. These in vitro results suggest the possibility that wobbler astrocytes act not on motoneurons directly bu t, rather, through other spinal neurons to induce motoneuron degeneration i n the wobbler disease. (C) 2000 Wiley-Liss, Inc.