Thursday, June 9, 2011

Getting My Brain Back -- In Praise of BDNF


Here is the star of Getting My Brain Back, the Neuron.  I've got lots of neurons.  So do you.  They are our friends and we need to take care of them, so they take care of us.  BDNF, brain-derived neurotrophic factor will help us do that.  How BDNF is giving me my brain back is our story for the day.  But first...

Preface

Did you notice?  I wrote a book report in April.  If you are a regular reader, I guess that is obvious.  Let me try again.

I read a book.  Not just the one by Agatha Christie.  Maybe you still don't get it.  Never mind.  Here is the story.


Introducing Neuron, The Brain Cell
 
To the right we have a line drawing of the neuron with its major parts.  Neurons are essentially communication devices.  Each one receives messages from another neuron and passes them on to the next.  Dendrites are like the receivers.  Yes, they look like kinky hair.  Today let's call them ears, one ear at the end of each little spine growing out of each branch.  Axons are senders.  They carry the messages to the next neuron.  Yes, the nerve endings look like feet.  Today let's call them mouths.

Now imagine each of these dendrites pressing its ear against the mouth of another neuron's ending, and each of these nerve endings pressing its mouth against the ear of the next neuron's dendrite.  A lot of action going on here!  A lot being communicated.  The dendrites/ears and nerve endings/mouths connect at synapses, where a chemical exchange occurs, which passes the information from one neuron to the other.  But the chemistry is a subplot, not to be detailed in this post. Maybe in a sequel, if this story goes well.

We Need Lots And Lots Of Dendrites And Axons

So the story begins.  Baby brain is born, with a cast of a million neurons, more or less, like the one above.  I like that line drawing.  I'm thinking of my neurons all lined up, dendrites and nerve endings touching, grooving on each other, a regular reggae party, Don't worry 'bout a thing.  'Cuz every little thing gonna be alright...

Just how many of these connections are there?  Notice lots of dendrites on the one cell body in this line drawing, with spines coming off branches, a dendrite at the end of each spine.  Some cells have just one dendrite.  In the cerebellum, the purkinje cells have about 100 branches and 60,000 spines on each branch, more or less.  That's 6,000,000 dendrites/ears/potential connections per cell.  Not all of baby's 1,000,000 brain cells are quite so crowded as the ones in the cerebellum.  But if we do the math, that adds up to a gajillion dendrites, give or take a few, a gajillion potential connections.

Pruning Dendrites -- Sometimes Less Is More

Okay, a gajillion connections is a lot of noise, even for a baby.  Baby's brain has work to do.  What tastes good when I bite it?  What hurts?  What doesn't hurt?  What gets mad and goes away?  Focus, kid!  That mad reggae party in there is great, but we need some focus!

So right off the bat, some of these connections get used a lot, and some start disconnecting.  At birth, baby will pay attention to anything.  Within a year, baby pays attention to people speaking the language (or languages) spoken in the house and gets bored by people speaking something else.  The rule of the house regarding dendrites is Use it or lose it.  The connections for all the other languages of the world die off, and the connections for baby's own language get reinforced.

This pruning of connections is how we develop habits, as the messages go down the same channels over and over, like chopping a path through the kudzu.  The next time we go that way, the chopping is already done.  We can get there faster, and have energy for whatever we want to do once we reach our destination.

Brain-Derived Neurotrophic Factor

But wait!  While you were standing there with the tape recorder, coaxing baby to coordinate lips and tongue and breath and come out with -- will it be mama or papa? -- BDNF was already on the scene.


Here is the co-star of Getting My Brain Back -- Brain-Derived Neurotrophic Factor.  BDNF is a protein, one of the neurotransmitters.  It is found in greatest concentrations in the hippocampus (memory, emotions, learning), cortex (thinking) and basal forebrain (which produces acetylcholine, another neurotransmitter used in learning).  Its job is to help cells grow, survive and differentiate.  It supports the dendrites, to strengthen existing connections and make new ones.

So Which Is It We Need, More Connections Or Less?

Both, of course.

I lost all my Spanish speaking dendrites when I was a baby, and painfully replaced them in high school, with the help of the protein designed to do just that, BDNF.  Then they fell into disrepair again for several years, until my spouse and I visited her high school foster family in Ciudad Obregon, Mexico.  Sra. Ramirez was teaching me some card game.  Only the rules seemed to change every turn.  I needed to repair those Spanish-speaking channels fast!  BDNF works, but not that fast.  That little old lady robbed me blind.

Stress Makes Things Happen

So we have our stars, Neuron and BDNF.  Now we need some plot.  Otherwise known as Stress.

Poor stigmatized and misunderstood stress.  How about for now, we rename it stimulation.  Here is what I mean.

Shiny new bicycle.  The five-year-old begs, Oh, please, please, please take the training wheels off!  It took a lot of begging.  It was made clear to me that once the wheels came off, they were not going back on.

Meanwhile, in the previous five years, the dendrite/axon connections in charge of balance were developing, as I learned to walk and even skip -- no mean feat!  But this was a new wrinkle on the task.  One step up onto those pedals, the other foot lifts off the ground.  Houston, we have lift-off.  And suddenly -- STIMULATION!!

The inner ear is going crazy, sending out urgent messages to the basal ganglia which is supposed to remember this stuff, like skipping.  And falling.  Remember falling?!  That sets amygdala, hypothalamus and pituitary into action.  Remember panic?!  Now the hippocampus gets the SOS.  This is a job for BDNF!

So inside hippocampus cells, the endoplasmic reticulum goes into BDNF production, and the dense-core vesicles start pumping the stuff out.  Time for some dendrite growth and support!

Nature/Nurture

What happens next is an interplay between the existing brain and its wider environment.

Nature: A normal hippocampus (here in red) looks like a sea horse or a curled up green bean, 1 1/2-2 3/4 inches long if stretched out. Depending on the genetic role of the dice and/or the stress experienced by the pregnant mother, and hence by the fetus who is along for the ride, some brains have smaller hippocampi right from birth, along with a diminished capacity to produce BDNF.

That is not necessarily a problem.  Little people can do big things, same with little hippocampi.  It depends on whether the demands for BDNF are matched by the capacity of the hippocampus to produce it.

Nurture: There is this perception out in parentland that shouting helps children to learn.  Actually, sometimes it does.  When the task is simple and the learner lacks motivation, like, how to take the dishes from in front of the television set and place them in the kitchen sink, an occasionally-used loud voice can be just the trick to stimulate the neurotransmitters needed for memory consolidation.  Downside -- this method loses effectiveness with frequent use.

Riding a bicycle, however, is not a simple task.  There is a lot of communication already going on inside the brain of the person who is trying with all her might not to hit the pavement.  That BDNF is pumping out just as fast as it can.  In this case, shouting adds more cortisol load to the hippocampus than is helpful.  It overwhelms the learning process and turns it into a survival process.

When stimulation crosses over to stress and from stress to terror, the brain has to get more efficient.  Learning is a luxury.  The over-stressed person falls back into what is familiar.  Like falling. 

Well, into every child's life, an occasional full adult meltdownage will fall.  Nobody will learn to ride a bike today.  But the brain is built with its own repair system.  BDNF will clean up the mess, and we will go back to bike-riding another day.

Overstimulation

Then there are those parents who think that nature is bad and that hitting is part of nurture.  Hitting is even less helpful than shouting for learning complex skills.  Hitting really overstimulates the brain.

Especially random hitting.  Unpredictable and random shouting and hitting disrupt the feedback circuits in the HPA (hypothalamus/pituitary/adrenal) axis.  Over time the HPA axis loses its ability to shut down when not needed.  Because it has learned that it never knows when it will be needed.  So it just pumps out that cortisol 24/7.  The hippocampus keeps getting the message and pumping out that BDNF, until it is depleted.  Learning stops.  The dendrites in the hippocampus itself atrophy and die.  Literally, the hippocampus shrivels.

Then that already-from-birth-little hippocampus gets smaller still, with even less capacity to produce BDNF to repair the damage.  Or learn to ride a bike.

As far as cycles go, this one is not good.

Getting My Brain Back Anyway

But.  Take away the shouting and hitting.  Take away the random and unpredictable.  Give the poor pitiful hippocampus a rest.  The brain comes equipped with its own repair system.  Give it a couple years.

Build some more implicit memory in the basal ganglia, more balance, more skipping.  How about some roller skating?  Stronger legs?

Then one day, go to some safe and sane spot.  Little bit at a time.  Push off.  Put a foot down.  Push off.  Put a foot down.  Over and over.  Nobody else knows how often the foot touches the ground.  Nobody gets bored or angry at this repetition that stimulates a new channel of communication from inner ear to hips and knees and shoulders.  Learn.  This is what the brain is designed to do.


I can ride a bike.

I Wrote A Book Report

In one long run-on sentence I will now slide by subsequent shouting, hitting and random adult meltdownage, resulting in hippocampal damage and over-sensitized HPA axis, followed by untreated episodes, inappropriately treated episodes, SSRI poisoning, countless chemistry experiments setting up insomnia, hypomania and hysteria, exacerbated by continual harassment and activation of HPA madness by the short-term disability carrier, terminating in brain damage and long-term disability.

Only, of course, that is not where it terminates.  The brain has its own built-in repair system, BDNF.

Take away the shouting  and hitting.  Take away the random and unpredictable.  Give that poor pitiful hippocampus a rest.  Give it a couple years.

I used to write books.  In 2005 I wrote most of the book Prozac Monologues in one week, and finished it in two more.  Well, maybe that was more a symptom than an accomplishment.  But still, it was written well.

Last year, on the other hand, I could not read a book.  The year before, I would pick up a magazine, like an airline magazine, read a sentence at random, read the sentence that came before it, remember you are supposed to read from the beginning, find the beginning, get halfway through the first sentence and lose interest.

But even that little pea pod hippocampus of mine can still produce BDNF.  Go to some safe and sane spot.  Push off.  Write a sentence.  Put a foot down.  Go empty (half) the dishwasher.  Push off.  Delete a prepositional phrase.  Collapse into an hour of BeJeweled Blitz on Facebook.  Write a paragraph.

Next day, rearrange the sentences of the paragraph.  Google something.  Half an hour later, try to remember what I wanted to know.  Delete the whole paragraph.  Quit for the day.

Over and over.  Nobody else knows how the writer wobbles, how often the foot touches the ground.  Nobody else gets bored or angry at this painful process that stimulates a new channel of communication from one part of the brain to the next, hippocampus, amygdala, facebook, frontal cortex, Pub Med, anterior cingulate cortex.

This is what the brain is designed to do, grow new dendrites to replace the ones that burned up in that fire, in all those fires of all those years.

I wrote a book report in April.  I am getting my brain back.

Afterword

If you have read the original (How the Brain Works), or God help me, wrote it, you may be disappointed to find major characters missing from this adaptation of the book to the blog post.  Given the name of the blog itself, Eli Lilly might marvel that serotonin did not get a mention.  Some other lab, ready to role out a new psych med, will protest that BDNF would be nothing without glutamate.  Me, I miss cousins Val and Met, who did get written, but whose paragraphs got left on the cutting room floor.  You dopamine channel fans, write your own story.

Gimme a break.  It's a blog post.


Golgi-stained Neuron with cell body, axon, and dendrites from Robert Huber and used under the Creative Commons Attribution-Share Alike 3.0 Unported license
Scott Foresman, the elementary education publisher released the line drawing of the neuron and parts into the public domain
photo of babies talking by P Pogo and used under the Creative Commons Attribution 2.0 Generic license 
Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute created the cartoon of BDNF and placed it in the public domain 
photo of child on bicycle by Jacob and Marlies and used under the Creative CommonsAttribution 2.0 Generic license
Wahington Irving created the image of the hippocampi based on an MRI, and placed it in the public domain 
photo of drill sergeant screaming taken by Corporal Shawn M. Toussaint and in the public domain
flair from facebook
photo of cyclist Giusto Cerutti from the Dutch Nationaal Archief and in the public domain
photo of woman on bicyle by pedrosimoes7 and used under the Creative Commons Attribution 2.0 Generic license

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