Sleeplessness

Can sleep loss kill brain cells?

Yes.

Like the kind when I pull an all-nighter for school or work?

Yes – if you are a mouse.

So why should I care?

Because if similar events befall people, you may really want to protect your sleep time – or at least how long you stay up.  It is starting to look like brain cells – especially particular, rather important brain cells – may not regenerate without enough rest.

What Was Actually Found?

The study was performed at Sigrid Veasey’s lab at Penn Medical School.  Mice were given no choice:  they first slept normally; were given shorter periods of sleep;  then were forced into taking a lot less sleep. The idea was to put the mice through an analogue of human shift work.

Veasey’s group then looked carefully at a tiny part of the brain called the locus coereleus.  That’s Latin for dark blue spot. The LC is famous to students of stress – which at this point should include most of the American population.

The LC is small. But it’s the main producer of norepinephrine (noraderaline.)  The blue spot’s been a major focus of anxiety and panic research for many years.

And that’s not all. It’s also critical to keeping us awake and alert.  So it’s important in sleep.  It’s important in memory production and processing, and figuring out where you are in three-dimensional space – what we call balance.  Panic, anxiety, stress, worry, arousal – all prominently involve the LC.

And in the shift-worked mice, prolonged wakefulness led to the death of 25% of LC brain cells.

What Does That Mean?

The conclusion drawn so far:  one of the main ways the body has of combating and controlling stress – in all its forms – begins to die without enough sleep.

This is ironic.  A major part of what helps keeps you awake starts to die if you’re awake too long – at least if you’re a mouse.

This is a potentially big deal.  It may relate to the problems of post-traumatic stress. Humans with PTSD have decidedly less LC neurons when they die.

Not that correlation is causality.  But you don’t want to lose LC neurons.  They perform too many functions.

What’s the Mechanism?

Veasey et al. hypothesize the problems relate to the sirtuin systems.  Sirtuins are proteins that have generated enormous interest for people, like Woody Allen, who want to live forever.  Sirtuins get turned on by long term, low calorie diets. Their protective effects seem to have something to do with low calorie diets making animals live a lot longer.  So they are presently beloved of  longevity researchers.

The Penn group found that short term wakefulness – the kind that most working Americans experience watching late night TV before work days – increases the production of sirtuin-3.  By contrast, prolonged wakefulness was associated with much, much less sirtuin-3 production.  The protein seemed to poop out if the mice were kept up too long.

And then some of their brain cells started to die.

What’s Really Going On?

Sleep is required for regeneration of tissues everywhere – not just the brain.  In many ways, the Penn study is an extension of the famous work of  Alan Rechtschaffen at the University of Chicago.  Rechtschaffen found that prolonged lack of sleep universally killed animals. Fortunately, he did not test people.

What Veasey is arguing is that that even intermittent lack of sleep – of the sort interns and residents and nurses and soldiers and many, many shift workers commonly experience –kills  important animal brain cells.  And, you don’t have to be up all the time for cell death to happen.

Of Mice and Men

Will these results prove true in people?

You can bet the grants to find out are being written and reviewed as you read this sentence.

Mice and men have a lot in common.  But mice live much shorter lives.  And our brains – despite the statements of some politicians – are  quite different from mice.

But mice are much easier to study.  They don’t require permission slips for informed consent.  They can be reared in genetically identical forms.  They’re small, easy to feed and breed.  And though they certainly don’t like the end results, you can get brain tissue from them far more readily.

Humans resist brain biopsies very vigorously.

But, humans may have several tricks up our sleeves that mice do not.  Our brains have depths of informational mysteries not yet glimpsed.

Still, when it comes to stress, we can learn much from animals. And sleeplessness looks like a big stress. Particularly if it provokes the death of cells that help keep us awake.

And aware.  And alert.  Transformed by pleasure and pain.  For the Locus Coereleus is an important part of the brain.  You want to keep those cells alive as long as you can.

So you’ll be alert to all the dangers out there – like not getting enough sleep.
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