| First Author | Zehnder T | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 2 | Pages | 108952 |
| PubMed ID | 33852851 | Mgi Jnum | J:313892 |
| Mgi Id | MGI:6716762 | Doi | 10.1016/j.celrep.2021.108952 |
| Citation | Zehnder T, et al. (2021) Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation. Cell Rep 35(2):108952 |
| abstractText | The mechanisms controlling the post-natal maturation of astrocytes play a crucial role in ensuring correct synaptogenesis. We show that mitochondrial biogenesis in developing astrocytes is necessary for coordinating post-natal astrocyte maturation and synaptogenesis. The astrocytic mitochondrial biogenesis depends on the transient upregulation of metabolic regulator peroxisome proliferator-activated receptor gamma (PPARgamma) co-activator 1alpha (PGC-1alpha), which is controlled by metabotropic glutamate receptor 5 (mGluR5). At tissue level, the loss or downregulation of astrocytic PGC-1alpha sustains astrocyte proliferation, dampens astrocyte morphogenesis, and impairs the formation and function of neighboring synapses, whereas its genetic re-expression is sufficient to restore the mitochondria compartment and correct astroglial and synaptic defects. Our findings show that the developmental enhancement of mitochondrial biogenesis in astrocytes is a critical mechanism controlling astrocyte maturation and supporting synaptogenesis, thus suggesting that astrocytic mitochondria may be a therapeutic target in the case of neurodevelopmental and psychiatric disorders characterized by impaired synaptogenesis. |
