Figure 5. Localization of Sortilin and PGRN in Different CNS Cell Types.

(A) Double immunohistochemistry for PGRN (green) and Sortilin (red) in adult mouse frontal cortex. The boxed area in the merge is shown at the right. Scale bar, 7 μm.

(B) Anti-PGRN staining of mouse frontal cortex from WT and Sort1−/− mice. In both cases vacuolar staining is prominent in neurons, and there is a trend to decreased vacuolar localization and increased diffuse neuropil staining in the Sortilin null samples. Scale bar, 7 μm.

(C) Anti-Sortilin staining of human frontal cortex from neurological healthy control and an FTLD-TDP case with PGRN mutation. Scale bar, 30 μm for top panels and 10 μm for bottom panels.

(D) Sortilin immunohistochemistry of the ventral horn in the mouse L5 spinal cord shows significant expression of Sortilin in motor neurons. Scale bar, 50 μm.

(E, F) Immunohistochemistry for PGRN in the ventral horn (VH) of L5 spinal cord transverse sections from mice that had unilateral sciatic nerve resection 7 days previously. Injury-induced PGRN expression is detected on the axotomized side, but not on the uninjured side in E. Significant co-localization of injury-induced PGRN with the microglial marker (Iba1) and is observed on the axotomized side (blue arrows in F), but not on the uninjured side. Less intense vacuolar PGRN immunoreactivity is detected in motoneurons (white arrows in F). Scale bars, 50 μm in E and 18 μm in F.

(G) The conditioned medium and cellular fraction of C13-NJ microglial cell line cultures were immunoblotted for PGRN and for Sortilin. PGRN secretion is prominent, and there is little Sortilin immunoreactivity.