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Al Stahler: Remembering

 

On both sides of your head … behind your eyes … in front of your ears … are your temples. Beneath your temples – inside your skull – are your brain’s temporal lobes.

When we perform a task – smell a rose, hear a tune, think a thought – the brain goes to work. Brain cells turn on and off, and energy flows … lots of energy: When we’re at rest, every fifth forkful of food is metabolized – “burned” – to keep the brain supplied with energy.

Researchers can, with instruments, look into the brain to see where energy is flowing. No matter the task, brain cells turn on and off in many parts of the brain. But, for any one task – hearing, smelling, remembering – there is usually one part of the brain where LOTS of cells turn on and off, LOTS of energy flows.



For memory tasks, the temporal lobes light up.

Suffering from Alzheimer’s (AWLTS-hie-merz) Disease (AD), people lose, among other things, their ability to remember.



Just how our brains put things in memory … and pull them out again … remains a mystery.

Brain cells are connected. Each cell talks directly to hundreds, thousands of others; they turn each other on and off. Memory likely involves making and breaking connections among brain cells.

Brain cells – all nerve cells – send messages with electricity. They also use “words” … not spoken words, but words made of molecules – clumps of atoms, glued together. The molecules are constructed as long strings, here and there sticky. The strings twist and bend, almost tie themselves up in knots. Where sticky parts come together, they bind – tightly. The long, stringy molecule bends and folds and glues itself into a specific shape, never to come apart … so long as nothing goes wrong.

You’re hiking along, when a message travels – electrically – along nerves from your ears to your brain: “Rattlesnake – very close!” The eyes confirm the message.

Electricity can carry a message long distances … ears to brain, even toes to brain. But – a tiny fraction of an inch before reaching a brain cell – the electrical message stops … it can go no further.

The nerve cell now translates the message into words – into molecules, which drift, that last fraction of an inch, to attach themselves – like pieces in a jig-saw puzzle – to the surface of the brain cell.

Figuring out what’s going on, the brain sends a signal to the adrenal glands, atop the kidneys, to squirt a specially-shaped molecule – adrenaline – into the blood.

Reaching the heart – fitting into the surface of a heart cell like a piece into a jig-saw puzzle – adrenaline tells the heart to beat faster.

Reaching the liver – fitting into its surface like a piece into a jig-saw puzzle – adrenaline tells the liver to pour energy-rich sugar into the blood.

Muscles gobble up this sugar … and put some distance between us and the rattler.

Given that jig-saw puzzle molecules can carry all sorts of messages … that the information lies in their shape … could it be that memory also involves molecules glued together in different shapes? Some combination of jig-saw shaped molecules … along with connections among brain cells … might remind us of the aroma of mom’s cookies. Another combination might remind us that two times two is four.

A problem with remembering things with molecules is that many molecules tend to be floppy – their sticky parts hold them together, but cannot stop them from flopping around; they might need help in holding their shape. So other molecules glue themselves onto these molecules, to keep them from flexing out of shape.

One such helper molecule is tau (rhymes with “cow”) protein.

If memory does, indeed, depend on shape, tau might be critical in keeping memory molecules in shape.

In Alzheimer’s patients, something goes wrong … rather than sticking to the molecules whose shape they’re keeping, tau proteins stick to each other, forming “tau tangles.”

Another molecule sits, not within the brain cell, but on its surface – in the membrane that surrounds the cell – the cell’s “skin.” (Touch your tongue to your cheek to feel the membranes of millions of living cells). Chunks of these embedded molecules sometimes break away.

Raw egg white is sloppy stuff. Molecules of egg white have a globular (roundish) shape, sliding easily among themselves. Like all proteins, those of egg white are long strings that have folded up and glued themselves together, to form their shapes.

Pop the egg into a hot fry pan, and the heat makes the egg white molecules unfold, and flop around. Sticky parts of the stringy molecule, ‘til now hidden away inside the folded-up molecule, find each other at random and stick, turning what had been sloppy egg-white into the firm white of a hard-cooked egg.

The chunks that break away from the brain cell’s membrane are also globular. Should they unfold – and lose their globular shape – they, too, can unfold, then re-fold, to congeal into stiff masses between brain cells: “amyloid plaques.”

Tau tangles and amyloid plaques stand out so sharply in the brains of Alzheimer’s patients, they make tempting targets in the quest for a cure. The U.S. Food and Drug Administration (FDA) has just approved another in a series of drugs that aim to reduce amyloid plaques. The approval has stirred controversy.

Any new drug must jump through hoops – lab tests and clinical trials – before it gains approval from the FDA. With no new drugs for Alzheimer’s having been approved in some years, FDA agreed to approve this new drug before all the hoops had been jumped through. Some of the studies are only now starting … results will not be seen for several years. FDA approval of the drug, before the hoops were passed through, has angered members of its advisory committee, and others.

A number of previous drugs have reduced amyloid plaques … without doing much to improve the patient’s condition … leading to the suspicion that the plaques are themselves a symptom of the disease, but not a cause of the problems. Something more fundamental may be causing both plaques and memory loss.

Which is not to say that a drug aimed at reducing plaques cannot be effective – it depends on its mechanism, its mode of action. If reducing amyloid plaques goes along with blocking the memory damage AD is doing, it can be helpful.

FDA seems to be hoping … as millions of AD-affected families are hoping … maybe this one will work. The new drug is NOT for every AD patient, and requires that a lot of tests be run, while it’s in use.

A friend is consulting working with a neurologist to manage her AD. I was excited to learn that the neurologist is recommending … exercise! Exercise is now being studied as a means of fighting AD.

Twenty-some years ago, researchers wondered if there could be a connection between not getting enough sleep, and later developing AD. They began tracking the sleep habits of folks who were then in their fifties. Now that those folks are in their seventies, the connection is unmistakable … skimping on sleep GREATLY increases the chances of AD, later in life.

Al Stahler enjoys sharing science and nature with friends and neighbors in The Union and on KVMR-FM. He teaches classes for both kids and grown-ups, and can be reached at a.a.stahler11@gmail.com

Tau tangles, between arrows, in a brain cell.
Photo by Mikael Häggström

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