How hibernation could help treat Alzheimer's

It is well known that during hibernation, when a mammal's core temperature cools to far below its normal level, brain cell connections are lost. Photo / 123RF

A mechanism that protects the brain when animals hibernate could help scientists develop new treatments for Alzheimer's and other neurodegenerative diseases.

Researchers believe a defect in the process may contribute to the death of brain cells in people with these disorders.

By simulating the effects of brain cooling in mice, they have uncovered a possible new target for drugs designed to block neurodegeneration.

Professor Giovanna Mallucci, who led the team from the Medical Research Council's Toxicology Unit, said: "We've known for some time that cooling can slow down or even prevent damage to brain cells, but reducing body temperature is rarely feasible in practice: it's unpleasant and involves risks such as pneumonia and blood clots.

"But, by identifying how cooling activates a process that prevents the loss of brain cells, we can now work towards finding a means to develop drugs that might mimic the protective effects of cold on the brain."

It is well known that during hibernation, when a mammal's core temperature cools to far below its normal level, brain cell connections are lost.

As the animal comes out of hibernation and warms up, the connections are reformed and normal brain activity is restored.

In humans, hypothermia - a significant reduction in body temperature - has been shown to protect the brain.

People have survived hours after a cardiac arrest with no brain damage after falling into icy water.

And artificially cooling the brains of babies that have suffered oxygen loss at birth is a technique employed to protect them against brain damage.

Cooling and hibernation lead to the production of molecules in the brain known as "cold-shock" proteins.

One, RBM3, has been associated with preventing brain cell death.

In the new study, the MRC scientists reduced the body temperature of healthy mice to 16-18C - similar to the temperature of a hibernating small mammal - for 45 minutes.

Mice do not naturally hibernate. But the scientists found the synapses - neural connections - in their brains still dismantled on cooling and regenerated on re-warming.

The researchers then repeated the experiment using mice bred to reproduce features of Alzheimer's and prion disease (a neurodegenerative disease caused by rogue prion proteins, such as CJD).

They found that the capacity for synapse regeneration disappeared as the disease progressed, accompanied by a loss of RBM3.

When levels of RBM3 protein were artificially boosted, this alone was enough to protect the mice and prevent synapse and brain cell depletion, reducing memory loss and extending lifespan.

Professor Hugh Perry, chairman of the MRC's Neurosciences and Mental Health Board, which funded the study, said: "The neuroprotective pathway identified in this study could be an important step forward.

"We now need to find something to reproduce the effect of brain cooling.

"Just as anti-inflammatory drugs are preferable to cold baths in bringing down a high temperature, we need to find drugs which can induce the effects of hibernation and hypothermia."

The research is published in the latest edition of the journal Nature.

- PAA