Emerging treatments targeting microglial states

1:16:01something called LTP, which is long-term potentiation. This is the idea that synapses will grow and shrink based on how they're how the neurons are talking to one another. This is this the the you know physical mechanism by which we learn. Like when we say our the connections are strengthening, literally what's happening is the size of the the synapses the connections is getting bigger and smaller. it's increasing in surface area and that's causing the connection to get strengthened. This is something that doesn't happen >> in um Alzheimer's. >> Okay. So, so what they did was they used they used these brain slices and they showed that if they have these manipulations where they downregulate

1:16:41PU1 using and then the CD28 comes out stuff like that you can restore >> this LTP you can restore this ability of the hippocampus to start forming connections and have a dynamic way of expanding connections contracting connections so on and so forth >> that is very >> so so there was a mechanistic link here >> to straight up learning Right. That that is that is tied to the >> and like and the hippocampus is the center for consolidation of memories, right? And the access to the long-term memories and things like that, right? So having this happen in hypocample slices is also super super important to show

1:17:21that you know this this is this could be a target for therapies in the future >> and and because you know the idea would be you want to try to target uh to the lowest level of abstraction possible. Yeah. >> Um, and [clears throat] because of like this again analogy of T-Rex with the brain, this seems to be an interesting place to target because it has so many derivative like it's like it's like it's at the foundation and then that is going to impact processes that happen at a higher higher orders and all that. So that that is interesting. Yeah. Yeah. So now when we look at translational horizons, it's promising but we have to be very very careful. Okay. One way to think about it was, okay, what if we just, okay, it depends on CD28, right?

1:18:02What if we just like stimulate CD28 and we boost these populations? Um, >> that sounds simple and biology is never that simple. There's actually this