SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells.

Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model.

Neuronal overexpression of Nogo receptor 1 in APPswe/PSEN1(ΔE9) mice impairs spatial cognition tasks without influencing plaque formation.

In the search for molecules that may alter the formation of amyloid-β (Aβ) protofibrils, it has been shown that the Nogo-system can interact and bind to amyloid-β protein precursor and thus affect the amount of Aβ that is formed and deposited in the brain. To further address this issue in vivo, we crossed mice that overexpress Nogo receptor 1 (NgR1), "MemoFlex", in forebrain neurons, with plaque forming APPswe/PSEN1(ΔE9) mice, to investigate if increased levels of NgR1 would influence plaque load or cognitive function in the resulting MemoFlex/APPswe/PSEN1(ΔE9) transgenic mice. We used a radial arm water maze and the Morris water maze to measure cognitive function.

Olfactory ensheathing cells promote neurite outgrowth from co-cultured brain stem slice.

Cell therapy aiming at the replacement of degenerated neurons is a very attractive approach. By using an established in vitro organotypic brain stem (BS) slice culture we screen for candidate donor cells, some of them being further functionally assessed in in vivo models of sensorineural hearing loss. Both in vitro and in vivo systems show that implanted cells face challenges of survival, targeted migration, differentiation and functional integration with the host tissue.

Nogo receptor 1 regulates formation of lasting memories.

Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests.