REBOUNDING BRAINS: Hibernating mammals offer scientists a unique way to study the brain's plasticity, as well as neurodegenerative diseases.
Image: Alan Vernon, via Wikimedia Commons
-
The Wisdom of Psychopaths
In this engrossing journey into the lives of psychopaths and their infamously crafty behaviors, the renowned psychologist Kevin Dutton reveals that there is a...
Read More »
Every September arctic ground squirrels in Alaska, Canada and Siberia retreat into burrows more than a meter beneath the tundra, curl up in nests built from grass, lichen and caribou hair, and begin to hibernate. As their lungs and hearts slow, the rivers of blood flowing through their bodies dwindle and their core body temperatures plummet, dipping below the freezing point of water. Electrical signals zipping along crisscrossing neural highways vanish in many areas of the brain. Seven months later the squirrels wake up and return to the surface—famished, eager to mate and perfectly healthy.
How hibernating mammals survive for so long at such low temperatures without any food or water beyond what they have stored in their own fat fascinates scientists for many reasons. Hibernation is an amazing biological feat and an opportunity to learn new ways of pushing the human body beyond its ostensible limits, as well as healing it when it breaks down. The arctic ground squirrel's brain, in particular, seems to be incredibly resilient. When ground squirrels hibernate their neurons shrink and many connections between neurons shrivel. But their brains periodically compensate for this loss with massive growth spurts, multiplying neural links beyond what existed before hibernation. Learning how the ground squirrel's brain recuperates could not only help scientists understand the brain's plasticity, but also suggest new ways to reverse or prevent cellular damage in neurodegenerative diseases. In particular, recent research on hibernating brains is changing the way some scientists think about misshapen tau proteins, which are a hallmark of Alzheimer's disease.
Brain freeze
Most small hibernating mammals—hamsters, hedgehogs, bats—turn down their body's thermostat during hibernation, relinquishing one of the defining features of all mammals: warm blood. Arctic ground squirrels are the most extreme example. In August 1987 Brian Barnes of the University of Alaska Fairbanks (U.A.F.) captured 12 arctic ground squirrels and implanted tiny temperature-sensitive radio transmitters in the animals' abdomens. He transported the squirrels to outdoor enclosures in Fairbanks—wire cages with borders reaching more than 1.2 meters belowground. By September the ground squirrels had dug burrows within the enclosures and begun to hibernate. Their body temperatures dropped to –2.9 degrees Celsius, almost three degrees below the freezing point of freshwater and probably the lowest core body temperature ever recorded in a living mammal. Despite this, ground squirrel blood remains liquid, most likely through a phenomenon known as supercooling.
In laboratory experiments, Barnes also measured the temperature of various body parts as the squirrels hibernated in a chamber kept at –4.3 degrees C. Although their colons, feet and bellies dropped below zero C, their necks never grew colder than 0.7 degree C, suggesting that the brain remains a little warmer than the rest of the body. Most mammals would die within hours if their brains were cooled so low, yet ground squirrel brains survived near freezing temperatures for weeks at a time. Every two to three weeks the squirrels shivered themselves back to their typical body temperature of 36.4 degrees C, which they maintained for 12 to 15 hours before becoming frozen pop-squirrels once more. Later, scientists would confirm that these intermittent periods of arousal are crucial to the ground squirrels' survival—without them their brains would wither long before spring's arrival.
Doom and bloom
Hibernation devastates the ground squirrel brain, wilting thousands if not millions of vital connections between brain cells, known as synapses. But its brain has evolved impressive resilience, repeatedly renewing itself at astonishing speeds, like a forest erupting through the scorched earth in a matter of days. Victor Popov of the Institute of Cell Biophysics in Russia discovered some of the earliest evidence of this plasticity. In the early 1990s Popov and his colleagues captured wild Siberian ground squirrels and kept them in temperature-controlled enclosures as they hibernated. The researchers sacrificed different animals at three distinct stages—during hibernation; two hours after one of the intermittent arousal periods; or one day after emerging from hibernation—and removed their brains to stain and examine the neurons within the hippocampus, an area crucial for memory. Neurons from squirrels that were in the middle of hibernation were shrunken and had far fewer dendrites—branches that receive signals from other neurons—compared with brain cells from fully awake and aroused squirrels. The dendrites in hibernating brains also had fewer dendritic spines, which jut out from the main branch like thorns on a rose stem and increase the number of possible synapses with nearby cells.
Whereas neurons in hibernating brains looked like barren tree limbs in the dead of winter, brain cells from squirrels that had just emerged from hibernation into a period of arousal sported dense crowns of overlapping dendrites. In only two hours the squirrels' brains had not only compensated for all the synapses lost during hibernation—their brain cells now boasted many more links than those of an active squirrel in the spring or summertime. One day later, however, their brains had pruned many of these ties, probably recognizing them as superfluous, much the way the developing mammalian brain shears its blooming neural forest.
Since Popov's study other researchers have observed similar loss and recovery of synapses in the brains of hibernating hamsters and hedgehogs. In a 2006 study Craig Heller of Stanford University discovered that the hibernating brain is incredibly plastic overall, not just in the hippocampus. Heller thinks that squirrels and similar hibernators lose dendrites during hibernation because their metabolism is too slow and their brains too cold and idle to keep those living wires in working condition.
Perhaps it's more efficient to let them shrivel, like a houseplant withering from neglect, and quickly nurse them back to life during those intermittent bouts of arousal. That way the mammals save as much energy as possible yet still preserve vital neural connections. Even so, researchers have estimated that many small hibernating mammals devote between 80 and 90 percent of all energy used during hibernation to keeping their brains alive.
Protective proteins?
Although scientists have documented structural changes to cells in the hibernating squirrel's brain, they do not yet understand what triggers the brain's recovery. Thomas Arendt of the University of Leipzig in Germany thinks the answer may involve a protein named tau. Normally, tau proteins help stabilize long, ropelike components of a cell's scaffolding called microtubules; tau keeps the many threads in the rope tightly bundled. When, for unknown reasons, tau proteins become hyperphosphorylated—that is, burdened with too many phosphate groups—they change shape and start clumping together inside neurons. As a result, microtubules grow slack and cells lose their shapes and stop functioning properly. Researchers know that misshapen tau proteins build up in the brain cells of people with various neurodegenerative disorders—notably Alzheimer's—but it is not yet clear whether distorted tau proteins in part cause such disorders or whether they are a side effect of the true causes.
Arendt and his colleagues discovered that hyperphosphorylated tau accumulates in the brains of hibernating European ground squirrels (Spermophilus citellus). The more synapses the rodents' brains lost during hibernation, the more hyperphosphorylated tau accrued in their neurons. Within a few hours of emerging from hibernation into a period of arousal, however, the squirrels somehow scoured tau from their brains. As one way of revealing this process Arendt stained slices of brain tissue from hibernating and aroused squirrels with a dye that binds specifically to tau proteins that carry extra phosphate groups. The difference was startling. Brain tissue from hibernating squirrels was generally dark and as black as ink in some areas, whereas tissue from aroused and non-hibernating animals was completely unblemished. Arendt thinks that hyperphosphorylated tau proteins accumulate during hibernation to prevent neurons from losing even more synapses than they do and, possibly, to play a role in the swift recovery of synapses during arousal. Hyperphosphorylated tau also accumulates in the developing mammalian brain, but largely disappears soon after birth, when the brain is pruning unnecessary connections. Perhaps, Arendt proposes, tau usually protects neurons, but malfunctions in the brains of people with Alzheimer's, analogous to an overreactive immune systems in people with autoimmune disorders.
Recently, Arendt and Barnes collaborated on a study that further investigated tau proteins in hibernating ground squirrels, hamsters and black bears. Clumps of hyperphosphorylated tau gathered in the bear brains during hibernation, even more reminiscent of the clusters of misshapen proteins observed in the neurons of people with Alzheimer's. Unlike ground squirrels and hamsters, black bears do not drop in body temperature much during hibernation nor do they enter periodic bouts of arousal. Rather, they remain in mild continuous hibernation all winter. Without intermittent arousals to clear hyperphosphorylated tau from their brains, Arendt proposes, hibernating black bears tiptoe perilously close to neurodegeneration, but somehow manage to reverse the damage when they wake up in the spring. Although these ideas about tau are controversial, Arendt and other scientists are pursuing related research because hibernating animals offer an opportunity to study Alzheimer's and related disorders in ways that would be unethical to replicate with the human brain.
Hibernating mammals may also give scientists a way to study the brain's untapped potential. Throughout history, neuroscientists have learned a lot about how typical brains work from brains that were unusual or damaged—organs that lacked the usual bridge of neural tissue between the two hemispheres or had large holes in a particular region. The hibernating brain, in contrast, reveals the extraordinary talents hidden in the typical mammalian brain. Some recent studies by Kelly Drew of U.A.F. and her colleagues suggest that even when a hibernating mammal is awake in the spring and summer its brain remains resistant to the kind of oxygen deprivation and neuronal damage that often result from heart attacks and stroke. When small mammals first evolved hibernation, their energy-hungry brains were put in an impossible situation: survive half the year with almost no oxygen or nutrition and emerge from the whole ordeal unscathed. Evidently, hibernation did not kill the brain—it only made it stronger.
Rights & Permissions
See what we're tweeting about
9 Comments
Add CommentVery interesting. It'd be most interesting to train these squirrels prior to hibernation and awakening. It's difficult to imagine that physical replacement of destroyed neural connections could reestablish acquired processes. Do the squirrels emerge from each hibernation as an infantile 'blank sheet of paper', or do they somehow retain past memories and acquired knowledge? It seems that these types of studies could reveal a great deal of general information about neuron connections and information retention...
Reply | Report Abuse | Link to thisWas dimethylaminoethanol (DMAE) tested for?
Reply | Report Abuse | Link to thisI read on DMAE in Life Extension, A Practical
Scientific Approach by Durk Pearson and Sandy
Shaw, Warner Books in the early 1990s and have
used it about half the time since.
As they explained it, DMAE acts like a detergent
to disolve lipofuscin, a dark pigment-like junk
composed of peices of fat and protein molecules
that clog, impair and eventually kill neurons
and other types of cells.
It is at the age of a human when the most and
fastest learning takes place DMAE production is
highest (that was age 10-11 for me, by nature).
After that DMAE production diminishes and event-
ually plummets in old age.
The dendrites of neurons clogged by lipofuscin
wither and break, thus brain cells lose their
connections to each other.
However, if DMAE and PABA (para-aminobenzoic
acid, a B vitamin), are taken together as a
supplement, dendrites regrow and new connections
are made between neurons.
I reccomend Twinlab DMAE and PABA drops because
they really did help me regain and surpass my
best childhood speed and volume of learning, with
deliberate effort. I have used this stuff more
than enough years, with and without other brain
nutrients and herbs, to know it works and does
not harm me. I do not lose the benefit in periods
when i don't have it, like now.
Pearson and Shaw say it's in anchovies, but i
recently enquired of Twinlab if it's vegetarian.
They insisted it is. It just starts to smell
a bit fishy due to slight oxidation after the
bottle has been opened many times. Lasts a long
time. I find P & S's reccomended daily dose
works best for me: 10 drops containing 100mg
DMAE & 150mg PABA, but i reccomend very low
doses of supplements to start. I mix it in
coffee, can't taste it then, but like many
B vitamin isolates, it tastes absolutely vile
strait. A couple of my freinds disregarded my
advice, squirted it directly into their mouths
and got a temporary lockjaw effect, but that
never happens to me because i always mix it
and don't take high doses. At 15 to 20 drops
a day it has some mild overdose effects and is
wasted. If i do 15, the next day i usually do 5
drops or none.
I have nothing commercially to do with any of
the above, but i ought to.
Maybe arctic squirells produce a lot of DMAE
& PABA when they come out of hibernation.
What a shame people - especially the elderly -
don't use more cheap brain nutrient supplements,
instead of what exhorbitant pharmaceuticals
drug companies eventually supply. I can't imagine
they could work as well.
Hi jtdwyer!
Comparing Skinnerian learned stimulus-response patterns before and after hibernation would tell us a lot about where and how memories are stored, but consider simple reflex or more complex "instinctual" response patterns to stimuli; assuming they're the same before and after (something else to test for!), how can supposedly hardwired response patterns possibly survive the massive rewiring described in the research? Does this indicate that specific synaptic connections are actually irrelevant to "knowing" what to do in a particular situation? Do the newly-regrown dendrites somehow restore the patterns of synapses that supposedly store patterns of memories? Where is *that* information stored?
Reply | Report Abuse | Link to thisPercival - Yes, it seems these results may conflict with current neurological hypotheses! Additional investigation seems to be necessary.
Reply | Report Abuse | Link to thisHi ultraharder!
Why, nagnostic? Following many of Pearson and Shaw's
Reply | Report Abuse | Link to thisreccomendations since the early 1990s, i became
objectively smarter than i was then. My reading,
writing, computing and inventing skills developed
phenomenally, with material results. Twinlab B-12,
good brands of Beta Carotene, E, C, senenium and
zinc help me that way. The same appear to cause
people who don't know, who i ask not to flatter
beforehand, to underestimate my age, typically 10
years or more. I have beaten a precancerous
condition i had four times and helped others beat
bad systemic cancers with these plus herbs.
Anyway, if you disagree with Pearson and Shaw,
it is no reason to dogmatically intimidate their
supporters. My mind is open to your criticisms
of them. I would entertain your reasons. My
approval of their reccomendations i have used
and shared up to twenty years is based on my
success with them, but i would think on what
you say.
Maybe what Nagnostic means is that Durk graduated from MIT with a triple major in physics, biology, and psychology, plus he has patents in the area of oil shale and tar sands recovery, lasers, holography and supplement formulations. Durk also assisted with equipment design and experiments for NASA's Space Shuttle. Someone that smart just ticks a lot of people off, so don't give it a second thought ultraharder.
Reply | Report Abuse | Link to thisPara-aminobenzoic acid is not a B vitamin. A quick search of reliable sources shows little value for taking it and a long list of possible side effects that can be fatal. The only proven use is topical sunscreen.
Reply | Report Abuse | Link to thisAside from it being used in a variety of industrial chemicals, dimethylaminoethanol has very little it has been shown to be useful for. Use to improve mental performance or suppress muscle spasms has been dis-proven.
Perhaps ultraharder is just smarter than ultraharder thought. As for Nagnostic, this is just one more post that has been removed.
"Why, nagnostic? Following many of Pearson and Shaw's
Reply | Report Abuse | Link to thisreccomendations since the early 1990s, i became
objectively smarter than i was then. My reading,
writing, computing and inventing skills developed
phenomenally, with material results. Twinlab B-12,
good brands of Beta Carotene, E, C, senenium and
zinc help me that way. The same appear to cause
people who don't know, who i ask not to flatter
beforehand, to underestimate my age, typically 10
years or more. I have beaten a precancerous
condition i had four times and helped others beat
bad systemic cancers with these plus herbs."
Correlation never shall nor ever will be synonymous with causation. This is one of the foundations of science.
If one were to attempt and see whether this treatment actually impacted the things you indicate it did, they would need to create a double blind trial with a control group given a placebo and an experimental group given the treatment prescribed. Then, and only then, could causality be shown beyond the shadow of doubt.
Travza,
Reply | Report Abuse | Link to thiscorrelation is not causation but may happen to
indicate it. You may consider my many times
repeated personal experience as anecdotal
evidence. I have personal proof of some
nutrients and herbs improving logic
performance. You can call that my subjective
experience and interpretation of it, but i
think everyone comes to beleive some things
the same way. I have not had DMAE and most
of my favorite supplements for some time
but (subjectively) they seem to have lasting
effect. My experience many times over shows
i do better with them. I am going to get them
in a few weeks and watch for results or none,
again. Pearson and Shaw use scientific method,
but i do not claim to. What i do is folk
medicine; cautious, considered, informal
experimentation. It may be compared to the
discovery of "4 Corners disease" on the big
Navajo reservation. Doctors found out that
was a rodent-transmitted hantavirus, but a
native healer was found who explained it
consistently with the medical discovery;
the symptoms, who was most vulnerable,
association with rodents. Her advice was
printed on pamphlets along with the MD's
advice that was consistent. Folk medicine
can work when it is based on long, repeated
experience, on informal experimentation.
That is how we got most of our original
pharmacopeia, much of which is still relied
on by MDs, since scientific method proves
certain chemicals in certain herbs folk
healers used for thousands of years work.
bucketofsquid (you mean Diogenes squid?), thank
you, i strive to get smarter as long as i live.
My subjective experience tells me certain
supplements as well as effort help. I read more
about PABA and DMAE since your post. Okay, PABA
is not a nutrient, but may be a synergist. Neither
have harmed me, together they sure helped me, as
well as i can subjectively tell. It's Twinlab
DMAE H3 drops i take. One of my friends got
lockjaw, the other a bad headache, but they
took it strait without measuring, perhaps a
dropperful. I always measure my doses, normally
10 drops a day. In some other subjects, i think
scientific method is the only way to find truth,
but if you personally find something works for
you, triple-blind studies with placebos don't
stand up to your own experience, as long as you
keep getting the same result.