After spending several years using various methods to deliver small molecules in the mouse brain in vivo, we have not achieved definitive success of chemical conversion inside mouse brains despite the observation of a few neurons after chemical treatment. This is rather disappointing, but we are still continuously trying direct in vivo chemical conversion in the mouse brain. The biggest challenge for in vivo chemical conversion is how to maintain a constant concentration of small molecules inside the brain without causing a severe invasive damage to the brain. We have tried using biomaterial to encapsulate small molecules, but, perhaps because our small molecules are too small or we have not found the right biomaterial for such small molecules, the small molecules we applied might not stay for a long time inside the brain. We also tried an osmotic minipump (Alzet) but the tip of the insertion caused significant tissue damage inside the brain, and the injury induced many DCX+ cells that were mainly reactive astrocytes 2 weeks after drug treatment (Figures S7I–S7K).
Shame, but this is an entirely understandable problem, and these are still early days!
On the other hand, during our vigorous testing of in vivo chemical reprogramming, we accidentally found that core drugs significantly increased adult neurogenesis in the mouse hippocampus (Figure 7). We initially injected core drugs through intracranial injection into the hippocampus and sacrificed the mice 7 days later (Figure 7A). We observed remarkable increase of DCX-labeled newborn neurons together with Ki67-labeled proliferative cells in the dentate granule layer (Figures 7B–7E).
So, not conversion of glia into neurons, but production of new neurons from progenitor cells. That's still really useful! The hippocampus is what gets whacked in a load of different brain disorders (wikipedia tells me Alzheimer's and other dementias, PTSD, schizophrenia, and depression, for starters), so being able to drive neurogenesis there sounds really useful.
its still debatable however if there is neurogenesis in the human hippocampus so not sure if this method results are transferable. it would be cool if it worked generally though. alzheimer's causes neuronal loss throughout the cortex, while parkinson's mostly on dopaminergic neurons.
After spending several years using various methods to deliver small molecules in the mouse brain in vivo, we have not achieved definitive success of chemical conversion inside mouse brains despite the observation of a few neurons after chemical treatment. This is rather disappointing, but we are still continuously trying direct in vivo chemical conversion in the mouse brain. The biggest challenge for in vivo chemical conversion is how to maintain a constant concentration of small molecules inside the brain without causing a severe invasive damage to the brain. We have tried using biomaterial to encapsulate small molecules, but, perhaps because our small molecules are too small or we have not found the right biomaterial for such small molecules, the small molecules we applied might not stay for a long time inside the brain. We also tried an osmotic minipump (Alzet) but the tip of the insertion caused significant tissue damage inside the brain, and the injury induced many DCX+ cells that were mainly reactive astrocytes 2 weeks after drug treatment (Figures S7I–S7K).
Shame, but this is an entirely understandable problem, and these are still early days!
On the other hand, during our vigorous testing of in vivo chemical reprogramming, we accidentally found that core drugs significantly increased adult neurogenesis in the mouse hippocampus (Figure 7). We initially injected core drugs through intracranial injection into the hippocampus and sacrificed the mice 7 days later (Figure 7A). We observed remarkable increase of DCX-labeled newborn neurons together with Ki67-labeled proliferative cells in the dentate granule layer (Figures 7B–7E).
So, not conversion of glia into neurons, but production of new neurons from progenitor cells. That's still really useful! The hippocampus is what gets whacked in a load of different brain disorders (wikipedia tells me Alzheimer's and other dementias, PTSD, schizophrenia, and depression, for starters), so being able to drive neurogenesis there sounds really useful.