Increased number and differentiation of neural precursor cells in the brainstem of superoxide dismutase 1(G93A) (G1H) transgenic mouse model of amyotrophic lateral sclerosis.

The superoxide dismutase 1(G93A G1H) (SOD1(G93A G1H)) transgenic mouse is a model of familial human amyotrophic lateral sclerosis (ALS) that has progressive neurodegeneration within the spinal cord and brainstem. In this study, we investigated the number and differentiation of neural precursor cells (NPCs). Nestin-positive NPCs were rarely seen in the nervous system of wild type controls or pre-disease mice at post-natal days 30 and 60. With disease onset on post-natal day 90, nestin labeled NPCs proliferated preferentially in the brainstem with maximal number and density at post-natal day 120. NPCs did not double-label with CNPase or O(4) markers of oligodendrocytes. The majority of the NPCs co-labeled with the astrocyte maker glial fibrillary acidic protein (GFAP) and a small number with the neuronal marker NeuN. At disease onset, 73 and 10% of NPCs co-expressed GFAP and NeuN respectively while at severe disease stage, 80 and 8% of the NPCs co-expressed GFAP and NeuN. Proliferating cell nuclear antigen (PCNA) was used to confirm that at least some of these cells undergo mitosis. Future studies could be directed at controlling the differentiation of these endogenous NPCs into neurons and astrocytes in order to ameliorate the degeneration within the brainstem of the ALS mouse.