In Mice, Autism-Like Behavior Connected to Problems Pruning Dendritic Spines
Spines on a dendrite
Autism spectrum disorders are associated with developmental abnormalities at excitatory synapses. Dendrites, the branched projections of neurons where electrical signals are passed from one cell to the next, are covered in hundreds to thousands of spines that facilitate the synaptic connections with other neurons. These spines are created and also pruned as part of normal learning and development.
Post-mortem examination of the brains of patients with autism spectrum disorders shows increased density of dendritic spines and less pruning in certain neurons in the temporal lobe. These examinations also show impaired mTOR autophagy. MTOR is a protein that plays a role in cell growth and survival. Autophagy is the normal process by which some components of cells are broken down.
A 2014 study by Guomei Tang et al. in the journal Neuron showed that mice that are genetically altered to have overactive mTOR also have reduced dendritic spine pruning, blockade of autophagy, and increased autism-like behaviors. An immunosuppressant drug called rapamycin inhibits mTOR, and treating the mice with this drug corrected the problems with spine pruning and the autism-like behaviors. (This was not true for mice who had been altered to have another type of autophagy.) Normal spine formation was not affected by the restored pruning ability.
Tang et al. concluded that mTOR autophagy plays an important role in dendritic spine pruning, and that restoring neuronal autophagy can correct synaptic abnormalities and restore normative social behavior in mice with hyperactive mTOR.
