Some of the symptoms of autism may be due to the brain failing to prune synapses during the early, crucial years of a child’s life. The resulting overabundance of synapses could contribute to some of the symptoms of autism and an understanding of the mechanisms behind this failure to prune may lead to future treatments for the condition.
A study by researchers from Columbia University Medical Center, reported in Neuron, found higher densities of dendritic spines in the brains of children and adolescents diagnosed with autism, compared those without that diagnosis. Dendritic spines are those parts of the neuron where synapses are found, the connections that carry signals between neurons. According to one estimate, each neuron contains on average around 7,000 synapses.
Synaptic pruning is a major feature of brain development. During infancy there is a massive increase in the number of synapses; the total number of synapses in a three-year old’s brain is estimated to be one quadrillion (1015). However, as well as producing massive amounts of new synapses, the child’s brain is also pruning these connections, relinquishing those that are seldom used. Experience-dependent pruning leads to a brain that is more organised, with its own unique set of connections, its own unique mind. This pruning continues throughout childhood and adolescence, so that by adulthood the brain has half or less of the number of synapses that it had at the age of three.
The researchers at Columbia looked at the brains of 48 children and adolescents who had died at ages ranging from 2 years to 20. Around half of these individuals had received a diagnosis of autism and half had not. The researchers were particularly interested in those areas of the brain that are associated with social interactions and communication.
The study found little difference when looking at younger children from both groups; both showed a similar density of synapses. However, the picture changed significantly by the late teens. Adolescents who were not diagnosed as autistic had on average 41% fewer synapses than the infants, showing that a significant amount of pruning had taken place. This was in contrast to a reduction in synaptic density of only 16% in children who had been diagnosed as autistic. It seemed that something had inhibited the synaptic pruning of these children.
An association between synaptic over-connectedness and autism could help to explain some of the symptoms of that condition. The researchers link this over-connectedness with issues such as the autistic child’s over-sensitivity, for example, to noise and social situations, and to a greater susceptibility to epilepsy.
The reduced level of pruning in the autistic children was associated with higher levels of the protein mTOR, a protein which inhibits autophagy, the process by which cells remove their damaged parts. The researchers found a greater presence of damage within cells taken from the brains of children affected by autism, implying an inhibition of autophagy. This inhibition could help to explain the reduced level of synaptic pruning in these children.
This hypothesis was tested with mice that had been genetically modified to develop tuberous sclerosis complex, a genetic condition often accompanied by autism. These mice showed social behaviours similar to autism in humans and also had raised levels of mTOR. Treatment with the drug rapamycin reduced the mTOR in these mice and also seemed to eliminate the abnormal social behaviours. It may be that the reduced activity of mTOR allowed for increased autophagy and a greater rate of synaptic pruning.
Rapamycin is a powerful immunosuppressant used in organ transplants. It’s use in treating autism is not recommended, because of its significant side effects. Also, some mice did not respond to the drug with changed behaviours, implying that a variety of mechanisms were responsible for these behaviours. Moreover, results found in mice with a rare genetic disorder are not immediately transferable to the wide range of autisms found in humans.
This is an important study that brings more understanding to the brain dynamics that may be associated with at least some autisms. The apparent link between autism and synaptic overabundance may contribute to the extreme sensitivity of some autistic children. Some of their behaviours can be seen as attempts to block out or dampen down the impact of an over-stimulating and overwhelming world.