Although many things have gone wrong in the autistic brain, scientists recently have been focusing on one of the most glaring: a surplus of connections, or synapses.
Neuroscientists reported Thursday that, at least in lab mice, a drug that restores the healthy “synaptic pruning” that normally occurs during brain development also reverses autistic-like behaviors such as avoiding social interaction.
“We were able to treat mice after the disease had appeared,” neurobiologist David Sulzer of Columbia University Medical Center, who led the study published in the journal Neuron, said in a telephone interview. That suggests the disease could one day be treated in teenagers and adults, “though there is a lot of work to be done,” he said.
A synapse is where one neuron communicates with another, forming functional circuits. 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,” Ralph-Axel Müller of San Diego State University said by e-mail. He has done pioneering work in overconnectivity and was not involved in the Neuron study, which he deemed “extremely exciting.”
According to the latest government estimates, one in 68 children in the United States has some form of autism.
For the new study, Columbia’s Guomei Tang painstakingly counted synapses in a key region of the cortex of 26 children with autism who had died from other causes and compared that to 22 healthy brains also donated to science.
In the autistic brains, synaptic density was more than 50 percent higher than that in healthy brains — and sometimes two-thirds greater.
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 behavior in the lab mice suggests that overconnectivity may be key.
Sulzer’s team used rapamycin, an immunosuppressant drug that prevents organ rejection and is sold by Pfizer as Rapamune. The team chose rapamycin because it works by inhibiting a protein called mTOR whose overactivity, the team found, inhibits synapse pruning.
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: Its wide-scale immune-suppressing effects likely would cause serious side effects.
“But there could be better drugs,” Sulzer said, 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,” Sulzer said.
In addition to government funding, the Columbia scientists received grants from the Simons Foundation. It was established by hedge fund pioneer and Renaissance Technologies founder Jim Simons, whose daughter was diagnosed with autism.