Figure 6.

GCM derived from TIMP-1 KO mixed glial (astrocytes and microglia) cultures poorly supports primary oligodendrocyte growth and differentiation. A, Primary oligodendrocyte precursor cells (A2B5⁺) were split and grown in either conditioned media collected from either WT C57BL/6 or TIMP-1 KO primary glial cultures. Immunocytochemistry for A2B5 and O1 following 5 d of culture revealed fewer A2B5⁺ cells, while O1⁺ cells exhibited a stunted morphology with smaller membranous fans of prospective myelin. B, Quantification of A2B5⁺ and O1⁺ cells confirmed a 65 and 74% decrease, respectively, in the numbers of cells grown in GCM derived from TIMP-1 KO mice. Error bars represent the mean ± SEM. **p < 0.01, *p < 0.05. C, Hypothesized model of TIMP-1 in the regulation of astrocyte functions during oligodendrocyte differentiation and CNS myelination. Our data indicate that astrocyte production of TIMP-1 functions directly to promote OPC differentiation. Coincidently, TIMP-1 also signals as an autocrine or paracrine factor on astrocytes that may too support OPC differentiation. An important effect of astrocytic TIMP-1 expression therefore is to enhance CNS myelination.