| First Author | Tang G | Year | 2014 |
| Journal | Neuron | Volume | 83 |
| Issue | 5 | Pages | 1131-43 |
| PubMed ID | 25155956 | Mgi Jnum | J:217829 |
| Mgi Id | MGI:5615870 | Doi | 10.1016/j.neuron.2014.07.040 |
| Citation | Tang G, et al. (2014) Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron 83(5):1131-43 |
| abstractText | Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2 +/- ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 +/- mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 +/- :Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR. |
