THE VAMPIRE APPROACH OF BRAIN REJUVENATION - A CURE FOR ALZHEIMER’S DISEASE?

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Will baby blood hit the anti-aging market? Is the young blood transfusion the new omega 3 / golgi berries for the prevention of cognitive decline? Stanford and Harvard scientists claim so. A new wave of interest was drawn from an old, yet neglected medieval medical technique, where two circulatory systems, one old and one young, were connected in order to refresh the old brain and facilitate its healing and rejuvenating mechanisms. The method, now fancily called heterochronic parabiosis, has recently been brought back to scientific focus for one simple reason: it looks like its working.


source: http://tinyurl.com/qcr9bwy

The neurological decline and associated cognitive deterioration experienced during healthy ageing as well as neurodegeneration is one of the biggest mysteries in neuroscience. It seems like we cannot point out a single, culpable black sheep from the several factors that accounts for the progressive decline in the end of life. Rather, it is more likely that there is a cascade of "little things going wrong" that leads to the decline in overall performance. This is exactly why counteracting or slowing down this progress is not an easy task.  It is not surprising that a method offering an all-purpose "cure" against old age will rob the bank, especially if it can have headlines such as Vampire therapy of ageing, and put Fifty shades of grey ads in the corner.

2014 was the year of young blood. I mean, apart from the season finale of True Blood, Katsimpardi and colleagues (2014) stitched an old and a young mouse together to connected their circulatory systems. This was not only beneficial for the vascularisation of the old brain compared to the young one but also upregulated the neurogenesis in one of the areas of the brain known for its role in the memory formation, the hippocampus. Pretty fascinating stuff, because it implies that we can now fight ageing in two ways: 1) better circulation in the brain (hence more food and oxygen to the neurons, and less probability of a stroke) and 2) more neurons in the area that is most likely to be the correlated with the contextual memory (decline). However, there is a rather big jump between the experimental evidence and literature review of possible candidate mechanisms to put behind all these effects. The authors finally pulled out the chocolate sprinkle (see the podcast) of growth factors called GDF11 to test on their parabionts. However, GDF11 is, according to my knowledge, too big a protein to cross the blood brain barrier (its concentration was not measured, it was only administered in the brain as a separate experiment). This does not mean that it cant account for a lot of circulatory beneficial effects, but I cant necessarily see the direct connection with the neurogenesis. The authors themselves highlight overall effects saying 

This suggests that neural stem cells exposed to young systemic factors increase their ability to proliferate and differentiate into neurons.

(highlighting by me if you cant tell form the shade of purple immediately :P)

Hhmmm...anyway... Are these newborn neurons functional parts of the network; can we correlate their operation with physiological and behavioural improvement? Stanford suggested that we can. This paper is an old-school, all rounder evaluation of the vampire approach, so much so that they are not even stitching the bellies together, just transfusing the serum of young mouse to older ones. Clever move, not just because it helps the PR part (stitching together old people with babies, not my dream advert for rejuvenation therapy), but it also makes the implementation easier. They also started by looking for the 'it' factor of rejuvenation by performing a genome-wide microarray analysis of the old and young hippocampi in the parabiont mice. They found a rather good chocolate sprinkle called Creb (cyclic AMP response element–binding protein), that is known for regulating game-changer proteins such as C-Fos (indirect correlate of neural activity), and to be essential for the sustenance of the good old LTP (see later). Now thats a start, but what else changed? If we compare levels of neuroscientific interest to a computer (dare I compare it to the brain itself), they found differences on all levels. If we take the hardware, they showed greater number of dendritic spines in the heterochronic parabionts in the dentate gyrus of the hippocampi, but not in another part (CA1). Sadly, the press was shouting Alzheimer, but in this neurodegenerative disorder, dentate gyrus stays intact for relatively long time.  Does not immediately shout Alzheimer to me. 

Difference of all levels (1. experimental groups, 2. anatomical remodelling: more spines (hardware), 3. change the physiological correlate of synaptic plasticity, more sustained LTP in the control group (software) )
source: http://tinyurl.com/qxhdm35

Anyway, the authors then addressed if there is anything upgraded in the software. They found that long term potentiation, the gold standard electrophysiological measure of long term memory function was maintained for the entire recording period in the old members of the old-young  pairs compared to the aged members of the old-old pairs (controls). We all know how slicework in neuroscience is the bread and butter of describing causality, but we know nothing about what happened in vivo from all this. Lastly, the IT wants to know what happens if we give a new task to this computer, so the behaviour of the heterochromic parabionts vs controls was tested in many, hippocampus-related contextual memory tasks. This tasks are basically the rodent version of the where did I park my car last night kind of lifehacks. Surprise, surprise, rejuvenated old fellow mice did better than re-not-juvenated peers. 

Now one last thought about this ... where is the evidence that it is a cure for Alzheimers??

Taken together, what can modern neuroscience say about the fountain of youth compared to the good old times? Not more than that we can actually prove the effect of young blood. Converging evidence supports the method is somewhat, somehow working. Exactly how my grandma argues for superstition and folk wisdom. It is still a good guess, we might as well give it a go, even without knowing the chocolate sprinkle factor of it. Even if we have no idea how to implement a huge amount of young blood transfusions on a longer term.