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Scientists shed light on the brain mechanisms behind a debilitating sleep disorder

October 10, 2013

TORONTO, ON — Nor­mal­ly mus­cles con­tract in order to sup­port the body, but in a rare con­di­tion known as cat­a­plexy the body’s mus­cles “fall asleep” and become invol­un­tar­i­ly par­a­lyzed. Cat­a­plexy is inca­pac­i­tat­ing because it leaves the affect­ed indi­vid­ual awake, but either ful­ly or par­tial­ly par­a­lyzed. It is one of the bizarre symp­toms of the sleep dis­or­der called nar­colep­sy.

“Cat­a­plexy is char­ac­ter­ized by mus­cle paral­y­sis dur­ing cog­ni­tive aware­ness, but we didn’t under­stand how this hap­pened until now, said John Peev­er of the Uni­ver­si­ty of Toronto’s Depart­ment of Cell & Sys­tems Biol­o­gy. “We have shown that the neu­ro-degen­er­a­tion of the brain cells that syn­the­size the chem­i­cal hypocre­tin caus­es the nora­dren­a­line sys­tem to mal­func­tion. When the noran­dren­a­line sys­tem stops work­ing prop­er­ly, it fails to keep the motor and cog­ni­tive sys­tems cou­pled.  This results in cat­a­plexy – the mus­cles fall asleep but the brain stays awake.”

Peev­er and Chris­t­ian Burgess, also of Cell & Sys­tems Biol­o­gy used hypocre­tin-knock­out mice (mice that expe­ri­ence cat­a­plexy), to demon­state that a dys­func­tion­al rela­tion­ship between the nora­dren­a­line sys­tem and the hypocre­tin-pro­duc­ing sys­tem is behind cat­a­plexy. The research was recent­ly pub­lished in the jour­nal Cur­rent Biol­o­gy.

The sci­en­tists first estab­lished that mice expe­ri­enced sud­den loss of mus­cle tone dur­ing cat­a­plec­tic episodes.  They then admin­is­tered drugs to sys­tem­at­i­cal­ly inhib­it or acti­vate a par­tic­u­lar sub­set of adren­er­gic recep­tors, the tar­gets of nora­dren­a­line. They were able to reduce the inci­dence of cat­a­plexy by 90 per cent by acti­vat­ing nora­dren­a­line recep­tors. In con­trast, they found that inhibit­ing the same recep­tors increased the inci­dence of cat­a­plexy by 92 per cent. Their next step was to suc­cess­ful­ly link how these changes affect the brain cells that direct­ly con­trol mus­cles.

They found that nora­dren­a­line is respon­si­ble for keep­ing the brain cells (motoneu­rons) and mus­cles active. But dur­ing cat­a­plexy when mus­cle tone falls, nora­dren­a­line lev­els dis­ap­pear. This forces the mus­cle to relax and caus­es paral­y­sis dur­ing cat­a­plexy. Peev­er and Burgess found that restor­ing nora­dren­a­line pre-empt­ed cat­a­plexy, con­firm­ing that the nora­dren­a­line sys­tem plays a key role.

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For more infor­ma­tion, con­tact:

John Peev­er
Cell & Sys­tems Biol­o­gy
Uni­ver­si­ty of Toron­to
Tel: 416–946-5564
Mobile: 647–207-7920
John.peever@utoronto.ca

Kim Luke
Com­mu­ni­ca­tions, Fac­ul­ty of Arts & Sci­ence
Uni­ver­si­ty of Toron­to
416–978-4352
Kim.luke@utoronto.ca