Transplantation of human glial progenitor cells into adult Huntington Disease mice rescues neuronal architecture and aspects of behavior

Glial pathology is a significant contributor to disease pathogenesis in Huntington disease (HD), and neonatal glial replacement can delay disease progression and rescue aspects of behavior in mouse models of HD. Here we asked if the transplantation of normal human glial progenitor cells (hGPCs) into adult HD mice might similarly ameliorate phenotype. We found that the introduction of hGPCs into the striata of adult R6/2 HD mice significantly ameliorated their motor and cognitive phenotypes, extended their survival, and rescued aspects of medium spiny neuronal dendritic architecture. To establish the basis for this effect, we used retrograde labeling of striatal MSNs with glycoprotein-deleted rabies virus in hGPC-engrafted adult R6/2 mice to discover that the dendritic architecture of striatal MSNs was partially restored in adult-engrafted mice. These findings suggest that glial replacement may delay disease progression in HD, and that this is associated with the dynamic reorganization of medium spiny neuron dendritic architecture. Overall design: WT mice or R62 mice (HD model) (n=2) were transplanted with human glia to investigate neuronal changes in response to glial transplantation. Unengrafted mice for both WT and R62 were used as control.