Children with autism have extra brain synapses

Children with autism have extra synapses in their
brain due to a slowdown in the normal brain
"pruning" process during development, say US
neuroscientists.
They found a drug that restores synaptic pruning
also reverses autistic-like behaviours in mice,
they report in the journal Neuron.
"We were able to treat mice after the [disorder]
had appeared," says study co-author
neurobiologist David Sulzer of Columbia University
Medical Center .
The findings suggest the condition could one day
be treated in teenagers and adults, "though there
is a lot of work to be done," he says.
The work is "extremely exciting", says Professor
Ralph-Axel Mueller of San Diego State University,
who was not involved in the research.
A synapse is where one neurone communicates
with another.
With too many synapses, a "brain region that
should be talking only to a select number of other
regions is receiving irrelevant information from
many others," explains Mueller, who has done
pioneering work in over-connectivity.
During brain development, a burst of synapse
formation occurs in infancy, particularly in the
cortex, a region involved in autistic behaviours;
pruning eliminates about half of these cortical
synapses by late adolescence.
For the new study, the researchers painstakingly
counted synapses in a key region of the cortex of
26 children and adolescents aged between 2 and
20 with autism who had died from other causes.
They compared that to 22 brains from children
without autism that were donated to science.
In the autistic brains, synaptic density was more
than 50 per cent higher than that in the brains of
children without autism and sometimes two-
thirds greater.
"It's the first time that anyone has looked for, and
seen, a lack of pruning during development of
children with autism," says Sulzer, "although
lower numbers of synapses in some brain areas
have been detected in brains from older patients
and in mice with autistic-like behaviours."
Over-connectivity
It is not clear if too many synapses are the main
reason for autism, but many genes linked to
autism play a role in synapse pruning. And the
discovery that synapse pruning reversed autistic
behaviour in the lab mice suggests over-
connectivity may be key.
The researchers traced the pruning effect to a
protein called mTOR. When mTOR is overactive
brain cells lose much of their self-trimming
ability.
"Almost all of our human subjects had overactive
mTOR and decreased autophagy, and all appear
to have a lack of normal synaptic pruning," says
Sulzer.
To restore normal synaptic pruning and reverse
autistic-like behaviours in mice, the researchers
administered rapamycin, an immunosuppressant
drug that prevents organ rejection and inhibits
mTOR.
However, even if the findings are confirmed -- and
Sulzer notes that treatments that work in lab
animals often fail in people -- it is unlikely that
rapamycin would be used in people with autism
because its widescale immune-suppressing
effects would likely cause serious side effects.
"But there could be better drugs," says Sulzer
"such as a molecule that dials up production of
synapse-pruning proteins."
One remaining puzzle is how the mice's brains, or
the drug, know which synapses to keep and which
to prune.
"But the mice started behaving normally" after
receiving the synapse-pruning drug, "which
suggests the right ones are being pruned," says
Sulzer.
Author - Deepak Kumar