Islamabad, DEC 07 (Online): A recent study in mice investigates immune cells called microglia in the developing brain. The authors conclude that the failure of these cells to perform an essential housekeeping role may lead to autism spectrum disorder in boys.
\nA recent study looks at microglia and autism spectrum disorder.
\nChildren with autism spectrum disorder (ASD) often display impaired social functioning, repetitive and inflexible behavior, and hypersensitivity to sound and light.<\/p>\n
Among 8-year-olds in the United States, about 1 in 59 (1.7%) has ASD.
\nHowever, research suggests that boys are four times more likely than girls to develop the disorder. About 2.7% of boys and 0.7% of girls have ASD.
\nWhy males are more susceptible than females has been a subject of debate among scientists, but a new study suggests that brain cells called microglia may be partly to blame.<\/p>\n
One of the functions of microglial cells in the developing brain is to engulf or \u201cprune\u201d redundant synapses. Synapses are the electrical connections between nerve cells.
\nNeuroscientists believe that synaptic pruning is essential for young brains to maintain their flexibility or \u201cplasticity.\u201d<\/p>\n
Overproduction of protein
\nResearch in mice has now found that the overproduction of protein in microglia \u2014 as a result of a genetic fault \u2014 prevents the cells from performing this vital housekeeping role, but only in males.
\nMale mice with this genetic quirk in their microglia display autism-like impairments in social skills and behaviors.<\/p>\n
This suggests that in some boys, the overproduction of protein in microglia during brain development may contribute to ASD.
\nThe research, which features in Nature Communications, was a collaboration between neuroscientists at Scripps Research in Jupiter, FL, and those at the Korea Brain Research Institute in Daegu, South Korea.<\/p>\n
\u201cOur study suggests that impairments in microglia play a key role in the development of autism behaviors, at least in some cases, and may help explain the higher prevalence of autism disorders in males,\u201d says senior study author Prof. Baoji Xu, Ph.D., of Scripps Research.<\/p>\n
Gene variants
\nScientists have linked hundreds of gene variants to ASD, but individually, they only raise the risk of developing the condition by a tiny amount. Some of these genes are inherited, while others are the result of new mutations.<\/p>\n
How the genes interact with each other and environmental influences to cause ASD remains poorly understood. However, a subset of ASD genes is known to increase protein production in cells via a common metabolic pathway, which these genes all disrupt in some way.
\nBetween them, the authors of the current study note, these particular genes account for about 3% of all ASD cases.<\/p>\n
Xu and his team set out to discover which type of brain cell causes ASD-like behaviors as a result of excessive protein production.
\nASD genes that increase protein production appear to do so via elevated levels of a molecule called eIF4E. The molecule is part of the mechanism for translating the protein-making instructions that our genes encode.
\nThe researchers genetically engineered mice to make abnormally high levels of eIF4E in either their microglial cells, their neurons, or another type of brain cell called an astrocyte.<\/p>\n
Only the mice with increased protein production in their microglial cells displayed the abnormal social behavior and cognitive deficits that are typical of ASD.<\/p>\n
Crucially, however, this was only the case in male mice.
\nWhen the team investigated further, they found that there were more synapses than normal in the brains of the male mice.
\nThey also noticed that the microglia in these males were less \u201cmotile,\u201d meaning that their movements were impaired. This may have disrupted the cells\u2019 ability to find and prune redundant synapses.<\/p>\n
Too many synapses
\nScientists have put forward the theory that a failure to remove excess synapses in the brain may be partly responsible for autism.
\nThe creation and strengthening of synapses occur during learning experiences as part of normal development.
\nHowever, the brain needs to retain some flexibility to allow it to take in new information and unlearn maladaptive behaviors.<\/p>\n
Having too many synapses in particular parts of the brain may create the sensory overload and repetitive, inflexible behaviors that are characteristic of ASD.<\/p>\n
Neuroscientists now believe that achieving a balance between learning and plasticity requires the removal of weak or redundant synapses during childhood and adolescence.
\nEven in adults, the removal of redundant synapses may occur every night as we sleep to retain a healthy degree of cognitive flexibility while we are awake.<\/p>\n
New treatments?
\nIn their article describing the research, the scientists conclude:
\n\u201cDeficits in synapse pruning would lead to the presence of excess, imprecise, and inefficient neuronal connections [\u2026] Our results show that elevating protein synthesis in microglia leads to ASD-like synaptic and behavioral aberrations in mice.\u201d<\/p>\n
A major drawback of this kind of research, however, is that animal models of disease may not accurately reflect how the disease works in people.
\nIn addition, as researchers have linked so many genes to autism, problems with synaptic pruning may explain some cases but not others.
\nNonetheless, the researchers are optimistic that their work will, one day, contribute to new treatments.
\nNext, they want to find out why increased protein production affects the microglia more in males than in females.<\/p>\n","protected":false},"excerpt":{"rendered":"
Islamabad, DEC 07 (Online): A recent study in mice investigates immune cells called microglia in the developing brain. The authors conclude that the failure of these cells to perform an essential housekeeping role may lead to autism spectrum disorder in boys. A recent study looks […]<\/p>\n
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