Summary of phenotypic findings
| Region and analysis | Birth | 1 mo | 2 or 5 mo | 1 or 2 yr |
|---|---|---|---|---|
| Whole brain | ||||
| Gross | No change (Fig. 1) | No change (Fig. 1) | At 2 mo, reduced size relative to control (Fig. 1) | At 2 yr, reduced size relative to control and 2-mo time point (Fig. 1) |
| Cerebellum | ||||
| Gross | No change (Fig. 1) | No change (Fig. 1) | At 2 mo, reduced size relative to control (Fig. 1) | At 2 yr, reduced size relative to control and 2-mo time point (Fig. 1) |
| Tissue area (histology) | NA | NA | At 2 mo, reduced relative to control (Fig. 3) | At 2 yr, reduced relative to control and 2-mo time point (Figs. 2 and 3) |
| PC loss (IHC) | NA | NA | At 2 mo, some potential loss of PC but highly variable (Fig. 4); at 5 mo, approximate 10% loss (Fig. 4) | At 1 yr, approximate 80% loss (Fig. 4) |
| Astrocytes/microglia (IHC) | NA | NA | At 2 mo, increased (Fig. 15) | At 2 yr, increased (Fig. 11) |
| Activated microglia (IHC) | NA | NA | At 2 mo, increased (Fig. 15) | At 2 yr, increased (Fig. 13) |
| Cortex/cerebrum | ||||
| Gross | No change (Fig. 1) | No change (Fig. 1) | At 2 mo, reduced size relative to control (Fig. 1) | At 2 yr, reduced size relative to control and 2-mo time point (Fig. 1) |
| Cortical thickness (histology) | NA | NA | At 2 mo, similar thickness to control (Fig. 3) | At 2 yr, reduced relative to control but not significantly reduced relative to 2-mo time point (Figs. 2 and 3) |
| Astrocytes/microglia (IHC) | NA | NA | At 2 mo, not increased (Fig. 15) | At 2 yr, increased (Fig. 10) |
| Activated microglia (IHC) | NA | NA | NA | At 2 yr, increased (Fig. 13) |
| Hippocampus | ||||
| Tissue area (histology) | NA | NA | At 2 mo, similar area to control (Fig. 3) | At 2 yr, reduced relative to control but not reduced relative to 2-mo time point (Figs. 2 and 3) |
| Astrocytes/microglia (IHC) | NA | NA | At 2 mo, not increased (Fig. 15) | At 2 yr, increased in CA region (Fig. 10) |
| Activated microglia (IHC) | NA | NA | NA | At 2 yr, increased in DG region (not statistically significant; Fig. 13) |
| Striatum | ||||
| Tissue area (histology) | NA | NA | At 2 mo, similar area to control (Fig. 3) | At 2 yr, reduced relative to control but not reduced relative to 2-mo time point (Figs. 2 and 3) |
| Astrocytes/microglia (IHC) | NA | NA | At 2 mo, not increased (Fig. 15) | At 2 yr, increased (Fig. 10) |
| Activated microglia (IHC) | NA | NA | NA | At 2 yr, increased (not statistically significant; Fig. 13) |
| Spinal cord | ||||
| Tissue area (histology) | NA | NA | NA | At 2 yr, reduced relative to control (Fig. 2) |
| Astrocytes/microglia (IHC) | NA | NA | NA | At 2 yr, increased (Figs. 11 and 14) |
| Activated microglia (IHC) | NA | NA | NA | At 2 yr, increased (Fig. 14) |
| Major axonal tracts | ||||
| Corpus callosum | ||||
| Astrocytes/microglia (IHC) Activated microglia (IHC) | Strong NHE6 protein expression (Ouyang et al., 2013) | NA | At 2 mo, no increase in astrocytes/microglia (Fig. 15) | At 2 yr, increased astrocytosis, microgliosis, and activated microglia (Figs. 9 and 12) |
| Anterior commissure | ||||
| Microglia (IHC) Activated microglia (IHC) | Strong NHE6 protein expression (Ouyang et al., 2013) | NA | NA | At 2 yr, increased microgliosis and activated microglia (Fig. 14) |
| Medial septum | ||||
| Microglia (IHC) Activated microglia (IHC) | Strong NHE6 protein expression (Ouyang et al., 2013) | NA | NA | At 2 yr, increased microgliosis and activated microglia (Fig. 14) |
CA, cornu Ammonis; DG, dentate gyrus; IHC, immunohistochemistry; mo, month or months; NA, not applicable; PC, Purkinje cell; yr, year or years.