Hibernating Animals Recover Lost Synapses
Bears, hedgehogs and ground squirrels will all be hibernating this coming winter as they always do. During their slumber the body cools, and to preserve resources in the energy-sapping brain, up to 30 percent of the synapses - the connections between neurons - disappear. Think of it as turning off the lights to save on your electric bill. Yet when the animals awaken months later, thanks to "cold shock" response proteins these synapses are replaced, and the animals return to activity with their cognitive faculties intact. This intrigued Prof. Mallucci, a neuroscientist from the University of Cambridge, because broken synapses are a classic early feature of neurodegenerative disease. If synapses can be regenerated in hibernating animals, perhaps they can be restored in humans.Cold Shock Proteins Vital for Synapse Health
Doctors have long known that cooling, or hypothermia, can protect the brain after a head injury, during cardiac surgery, and to prevent newborns from suffocating during delivery. But they don’t know why cooling has this effect. So, Prof. Mallucci and her research team carried out a series of experiments on mice -- who don't hibernate -- to see what happens to their synapses when put into an artificial state of hypothermia. In healthy mice, the scientists discovered, a quarter of synapses in the hippocampus -- a key memory center -- were lost, but then restored when their body temperature was returned to normal. Then they repeated the experiment in a model of mice that eventually succumb to Alzheimer's, and another group that develop prion disease, another name for neurological diseases that can lead to dementia and memory loss. First, researchers cooled and reheated the mice well before synaptic loss and symptoms occur. In this scenario, synapses recovered completely. But when researchers repeated this process just before synaptic loss was expected, the procedure did not prevent their launch into downward decline. The reason for this, they discovered, is that a cold shock protein called RBM3 rises in the healthy mice and in those in the early stages of disease, but doesn't do so in later stages of neurological disease.RBM3 Even Helps Mice Live Longer
Other experiments showed that early cooling and hibernation in early prion disease is highly protective as the rodents age. Early cooling and hibernation stops the loss of synapses with disease progression, preserves synaptic transmission, reduces neuronal death, maintains normal behavior, and on top of that the mice also live longer. All these benefits are lost however when RBM3 is simultaneously held down by artificial means. In the final experiments, RBM3 expression was artificially boosted without cooling in the mice affected by early prion disease. This achieved the same benefits as early cooling. Boosting RBM3 also allowed complete recovery of synapses after cooling in both neurodegenerative disease mouse models. But when the cold shock protein was suppressed, the disease progressed faster in both models. Even healthy mice lost synapses and memory, suggesting RBM3 plays an important role in normal synapse health. Prof. Mallucci and her team published their study in the journal Nature in 2015 where it was lauded as a major breakthrough in dementia research. In a BBC radio interview, Prof. Mallucci said she would like to carry out a human study but doubted whether an ethics committee would give its approval, because it would mean subjecting people to regular and potentially hazardous bouts of hypothermia. Fortunately, a listener came to the rescue.Cold Induces RBM3 in Humans
After hearing the interview, this listener reached out to Prof. Mallucci to say he was one of many regular cold-water swimming enthusiasts who voluntarily made themselves hypothermic, so they’d be an ideal group for her research. And so, over three winters, the scientists tested for the cold shock protein in the swimmers while using practitioners of tai chi as a control group. Standing before the volunteers at the poolside on the 19th of October, 2020, Prof. Mallucci told the swimmers, "We compared you to a bunch of people doing tai chi who didn’t get cold and none of them got increased levels of this protein. But many of you did. "It tells us that cold does induce this protein in humans. You’re the first non-patient cohort to show that cold water swimming raises this protective protein."Can You Try “Cold Shock Therapy?”
Unless you’re already a winter weather swimmer, you should know that sudden temperature lowering is a two-edged sword: it can damage as well as benefit the body. When extreme cold shocks the body it causes rapid breathing, a dramatic rise in heart rate and blood pressure, and has the potential to shut organs down. As a result, cold shock therapy is not a practical or safe approach to prevent or treat dementia at the moment. So, the next challenge for the scientists is to definitively show that the protein delays or reverses dementia, and if it can, to find a drug that will stimulate its production. Even if it were safe, I’m not sure there would be a rush among seniors to take a plunge into icy cold water. I might prefer to take my chances on dementia, or look for a kinder treatment. It makes me think of the skinflint Jack Benny’s famous response to the line, “Your money or your life.” He said he had to think about it.