Surplus neurons could cause neurodevelopmental disorders
19 Mar 2014 by hhwdjwbphm.d hhwdjwbphm.d
Autism could be caused by cells called microglia failing to trim unnecessary connections between neurons.
Researchers from EMBL and the Istituto Italiano di Tecnologia (ITT) found that by trimming surplus connections in a developing brain, microglia allow remaining links to become stronger. However, if this trimming fails to happen at the crucial stage of development, those regions are subject to a weaker communication network, which has lifelong effects on behaviour.
The team used fMRI to analyse the strength of connections in the brains of mice genetically engineered to have fewer microglia during development. The resulting three-dimensional maps of the functional connections showed mice with fewer microglia had weaker connections between neurons and less cross-talk between different brain regions.
“We study how events during the early postnatal period in mice affect brain wiring and behaviour in the adult animal,” lead researcher Cornelius Gross told Laboratory News. “The early postnatal period in mammals is a time when most of the synapses are formed and we became interested in a possible role of microglia in the pruning of unwanted new synapses during this period because we found that neurons “talk” to microglia during this time via a chemokine called fractalkine. When we break this communication (Cx3cr1 knockout mice) we get mice with a brain that has more connections but that are more weakly connected.”
The mice also displayed behaviour commonly associated with autism spectrum disorders and spent more time repeatedly grooming themselves and shunning social interactions.
“We show that a deficit in microglia during development can have widespread and long lasting effects on brain wiring and behaviour,” said Gross. “It leads to weak brain connectivity, decreased social behaviour and increased repetitive behaviour, all hallmarks of autism.”
“This is an exciting time to be studying microglia, they’re turning out to be major players in how our brain gets wired up,” he added.
The study has been published in Nature Neuroscience.
