A novel population of progenitor cells expressing cannabinoid receptors in the subependymal layer of the adult normal and Huntington's disease human brain

Abstract

Progenitor cells in the adult human brain subependymal layer are capable of producing new neurons and glial cells that may be useful as a source of cells for endogenous cell replacement for regions of the brain that undergo degeneration due to a neurodegenerative disease such as Huntington's disease, Parkinson's disease or Alzheimer's disease. We have previously demonstrated that in the human Huntington's disease brain there are increased numbers of progenitor cells proportional to the severity of the gene defect responsible for the disease and proportional to the severity of the pathology of the disease. One of the criticisms of a potential endogenous progenitor cell replacement therapy has been that the endogenous progenitor cells also contain the Huntington's disease gene and would therefore be just as susceptible to degeneration as those in the degenerate brain region. In the present study we have demonstrated the presence of cannabinoid CB1 receptors, which are preferentially lost in Huntington's disease, colocalised with the proliferative marker PCNA in the adult normal and Huntington's disease subependymal layer. This population of CB1 positive cells only colabels with PCNA and not with neuronal, glial, microglial or oligodendrocyte markers. These results indicate that the subependymal layer in Huntington's disease contains a subpopulation of proliferating cells that are also CB1 receptor positive and are thus not immediately susceptible to the neurodegenerative process that denudes the striatum of CB1 receptors. This finding raises the intriguing possibility that these cells could provide a suitable source of cells for the endogenous replacement of cells lost due to neurodegenerative disease.