LACK of sleep could be worse for

the body than we thought, at least

if humans react to it in the same

way as rats do.

Tarja Porkka-Heiskanen of the

University of Helsinki, Finland,

and her team discovered that rats

seem to mount an immune

response to sleep deprivation,

producing molecules that

ordinarily are associated with

stress. This suggests that chronic

sleep deprivation could lead to

stress-related illness, such as

heart disease, for example.

Porkka-Heiskanen’s team was

studying how the brain triggers

“recovery” sleep to overcome the

effects of sleep loss. Their earlier

work in rats had shown that levels

of nitric oxide increase in the basal

forebrain during periods of sleep

deprivation and that this plays a

role in prompting recovery sleep.

They had also found that an

enzyme called nitric oxide

synthase (NOS) was responsible

for jump-starting the production

of nitric oxide.

But where was the NOS

enzyme coming from? Porkka-

Hieskanen had expected that the

NOS produced by the brain would

be in a so-called “constitutive

form”, in other words, it would be

made regardless of the need for it.

Instead, her team found

that the NOS was in an “inducible

form” (iNOS) which is usually

produced when the body mounts

an immune response to stress

(European Journal of Neuroscience, DOI: 10.1111/j.1460-

9568.2006.05019.x). “This was

a big surprise,” says Porkka-

Heiskanen. “It means that the

body experiences sleep

deprivation as some kind of

hostile threat.”

The researchers also found

that the rats began producing

iNOS after being deprived of sleep

for just 10 minutes. “So even short

periods of sleep deprivation are

able to create this reaction,” says

Porkka-Heiskanen. “If it becomes

chronic, we are really putting a big

strain on the body.”

There is no direct evidence to

suggest that chronically high

levels of iNOS are dangerous. But

a 2004 study of healthy adults

aged between 26 and 38, who had

only 4.2 hours sleep for 10

consecutive nights, hints at the

dangers. Levels of a molecule

related to iNOS called C-reactive

protein were raised in the

volunteers – a strong predictor of

heart disease. Anil Ananthaswamy �

Why we’re not immune to losing sleep

VIRAL stowaways hidden in the DNA

of mammals could be more than just

idle passengers – they could be

crucial for fetal development.

Endogenous retroviruses (ERVs)

typically account for 8 to 10 per cent

of mammalian DNA, including our

own, but until recently were thought

to be relics of infection dumped in

the genetic equivalent of the attic.

Lab studies had suggested

that the endogenous Jaagsiekte

sheep retrovirus (enJSRV) might

help the early embryo implant in

the uterus and transform it from a

clump of cells into a shape from

which the placenta can develop.

To test this notion in live animals,

Tom Spencer and his colleagues at

Texas A&M University in College

Station, injected the uterine linings

of ewes with a drug that blocks the

activity of enJSRV. Pregnant sheep

given the virus-blockers miscarried

(Proceedings of the National Academy of Sciences, DOI: 10.1073/

pnas.0603836103).

Spencer believes that enJSRV

probably incorporated itself into the

genome of some sheep by chance

following an infection, and that it

may then have shaped the evolution

of the placenta by producing a

protein that was better at

orchestrating the early stages of fetal

development than the sheep’s own

protein. Eventually, the enJSRV

became part of every sheep’s

inheritable DNA, he says.

EnJSRV has a human counterpart

called HERV-W, which is thought to

play a similar role in embryonic

development. By finding out more

about how enJSRVs function in

development of the sheep placenta,

Spencer’s team hopes to throw light

on how defects in the process might

trigger miscarriages in women.

Robin Weiss, who studies ERVs at

University College London, points out

the usefulness of the sheep studies,

because you can’t switch off

expression of the HERV-W gene

in women to see if it triggers

miscarriage. “So this is an animal

study showing what we’ve kind of

Hitch-hikers that help a fetus survive

–Sick and tired?–

B. B

IRD/

CORB

IS

known about in humans.”

Manipulating ERVs could also

yield new ways of treating viral

infections, since ERVs are also known

to protect against infection with

certain viruses. In sheep, for

example, enJSRVs block the life cycle

of related but infectious JSRVs which

cause lung cancers and pneumonia,

and which killed Dolly the cloned

sheep. None of the retroviruses

“adopted” by the human genome

has any surviving infectious

counterpart, suggesting that our

adopted viruses have “won” the

battle for us and wiped out viruses

that were previously infectious,

says Spencer.

The tantalising implication is that

in the future, today’s viruses will be

adopted by our DNA and help protect

us from killers such as HIV and

hepatitis B. Andy Coghlan �

“The viral stowaway was better

at orchestrating the early stages

of fetal development than

the sheep’s own protein”

www.newscientist.com 16 September 2006 | NewScientist | 9

“The body experiences sleep

deprivation as some kind of

hostile threat, mounting an

immune response as if to stress”

060916_N_p8_p9.indd 9060916_N_p8_p9.indd 9 12/9/06 5:20:07 pm12/9/06 5:20:07 pm