Cold Shock Proteins and Neurodegeneration

You may be familiar with the research interest in heat shock proteins and their role in cellular health and repair. They are a part of the reaction to heat necessary to allow individuals to survive high temperatures. There is an analogous but different reaction to the other end of the temperature scale, also intended to assure survival under potentially damaging low temperatures. Here is an interesting result in which researchers investigate some of the mechanisms involved in the cellular reaction to cold, arising out of the study of hibernation in mammals:

It has long been known that during hibernation, where a mammal's core temperature cools to well below normal body temperature, synapses (the connections between brain cells) are depleted. This allows the animal to enter a state of 'torpor', similar to a very deep sleep but where no brain activity occurs, allowing the animal to survive without nutrition for weeks or months. As the animal comes out of hibernation and warms up, connections between brain cells are reformed and the number of synapses once again rises, restoring normal brain activity. In humans, a reduction in body temperature (hypothermia) is known to protect the brain. For example, people have survived hours after a cardiac arrest with no brain damage after falling into icy water. Artificially cooling the brains of babies that have suffered a loss of oxygen at birth is also used to protect against brain damage.

Cooling and hibernation lead to the production of a number of different proteins in the brain known as 'cold-shock' proteins. One of these, RBM3, has been associated with preventing brain cell death, but it has been unclear how it affects synapse degeneration and regeneration. Knowing how these proteins activate synapse regeneration might help scientists find a way of preventing synapse loss, without the need for actual cooling.

Researchers reduced the body temperature of healthy mice to 16-18ÂșC - similar to the temperature of a hibernating small mammal - for 45 minutes. They found that the synapses in the brains of these mice, which do not naturally hibernate, also dismantled on cooling and regenerated on re-warming. The team then repeated the cooling in mice bred to reproduce features of neurodegenerative diseases (Alzheimer's and prion disease) and found that the capacity for synapse regeneration disappeared as the disease progressed, accompanied by a disappearance of RBM3 levels. When the scientists artificially boosted levels of the RBM3 protein they found that this alone was sufficient to protect the Alzheimer and prion mice, preventing synapse and brain cell depletion, reducing memory loss and extending lifespan.



Nice! Maybe we have here a new compound useful for standby in cryonics.

Posted by: Antonio at January 15th, 2015 9:12 AM

Actually, the last line suggests that the compound should be tried on humans with neurodegenerative problems right now.

Posted by: Slicer at January 15th, 2015 10:54 AM

There is likely significant cancer risk associated with external consumption of RBM3. I would be wary of experimenting without sufficient animal and stage 1 human clinicals.

Posted by: Boudica's Baby at January 15th, 2015 1:50 PM

A lot of people would, given the choice, take that risk with a smile. In fact, this research suggests an even less medically recommended method for protecting against this kind of degeneration, and if I had the first stages of Alzheimer's and no other options, I might simply decide to go outside for a late-night walk wearing a T-shirt, maybe lay my head down in the snow for a while. What's the worst that could happen? Fatal hypothermia? Anyone who's seen Alzheimer's sufferers up close might see freezing to death as a mercy.

When you have "extreme risk of death" on one hand and "a guaranteed slow and horrible death" on the other, it's not hard to see why people might prefer the former. There's a reason why a disproportionate number of the elderly choose quicker ways out.

Posted by: Slicer at January 15th, 2015 7:08 PM

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