Research sheds new light on autism
Research by scientists from the Centre for Brain Research at the University of
Auckland is uncovering new information about the mechanisms underlying autism
spectrum disorders (ASDs).
behavioural manifestations of ASDs are well documented and include impaired
communication and socialisation, learning difficulties, and repetitive or
stereotyped behaviours. These behavioural characteristics are in turn
associated with a wide range of gene mutations. Many of these mutated
genes are responsible for the production of specific proteins in the neurons of
the brain. Dr Johanna Montgomery and her team took a very close look at
parts of these neurons – the synapses – to see what might be happening there.
The results of their endeavours are about to be published in the prestigious
Journal of Neuroscience.
Synapses are the structures that enable brain cells to communicate with each
other. This cell to cell communication is vital for a healthy brain, and it
underlies how we learn, remember, move and sense. In a complex
cascade of chemical and electrical signalling, information is transmitted from
one neuron to another at synapses. This process is mediated by several
families of protein, some of which form the bedrock of the synapse on the
‘listening’ side. Dr Montgomery’s team chose to investigate one of these
proteins, known as Shank3, because it has been identified as vital to the
communication process between two neurons, and is known to be mutated in ASDs.
Usually, the more two neurons ‘talk’ to one another, the larger and more
efficient the synapse becomes - in the same way that exercising your
muscles helps make them bigger and stronger. However, Dr Montgomery and
her team found that in neurons carrying ASD mutations in the Shank3 protein,
cell-cell communication was not only weaker than usual, but that repetition
didn’t strengthen or stabilise the synaptic connection.
Further investigation revealed that Shank3, when healthy, forms complexes with
two other types of protein known as neurexin and neuroligin (also frequently
mutated in ASDs). These complexes act to physically bridge the synaptic
gap and can transmit information from the receiving or ‘listening’ side of the
synapse to the transmitting side. This ‘backward’ flow of information
completes a feedback loop between the two neurons which is likely to be
responsible for the strengthening of the connection.
Dr Montgomery and her team theorise that the Shank3/neurexin/neuroligin complex
is critical to the ability of neurons to effectively transfer information across
the synapse to ensure the correct messages get through at the appropriate
strength. This complex of proteins helps both sides of the synapse
co-ordinate to improve the efficacy of messaging, and this in turn increases the
likelihood of successful transmission in future. Therefore, ASD mutations are
preventing this efficient transfer of information between neurons, which likely
underlies the behavioural and cognitive changes that occur in people with ASDs.
Intriguingly, the opposite occurs when neurons express multiple copies of the
Shank3 gene, as is known to occur in Aspergers Syndrome. In this case the
communication between neurons gets much stronger, increasing their efficacy and
providing a possible mechanism for the enhanced cognitive function that is
associated with this syndrome.
“This is really exciting stuff”, says Dr Montgomery. “We’re moving beyond
simply what happens in ASDs and starting to understand how it happens. Now
we have identified the problems that these mutated proteins cause, we have a
focus for developing treatments to offset the synaptic deficits that result.
That’s the next step.” Autism NZ Chief Executive Alison Molloy says, “It
is great that this research is happening in New Zealand. For those on the
autism spectrum, and their families, it means we can look forward to a time when
the characteristics of Autism can be managed, making living and communicating
considerably less stressful for them.” This research programme is funded
by grants from the Neurological Foundation of New Zealand and the Auckland
Medical Research Foundation.
Prepared by Sara Reid. Queries to
Thursday, 25 October 2012