| First Author | Chen L | Year | 2021 |
| Journal | Transl Psychiatry | Volume | 11 |
| Issue | 1 | Pages | 186 |
| PubMed ID | 33771970 | Mgi Jnum | J:350902 |
| Mgi Id | MGI:6808326 | Doi | 10.1038/s41398-021-01303-z |
| Citation | Chen L, et al. (2021) Pten is a key intrinsic factor regulating raphe 5-HT neuronal plasticity and depressive behaviors in mice. Transl Psychiatry 11(1):186 |
| abstractText | Serotonin (5-HT)-based antidepressants, selective serotonin reuptake inhibitors (SSRIs) aim to enhance serotonergic activity by blocking its reuptake. We propose PTEN as a target for an alternative approach for regulating 5-HT neuron activity in the brain and depressive behaviors. We show that PTEN is elevated in central 5-HT neurons in the raphe nucleus by chronic stress in mice, and selective deletion of Pten in the 5-HT neurons induces its structural plasticity shown by increases of dendritic branching and density of PSD95-positive puncta in the dendrites. 5-HT levels are elevated and electrical stimulation of raphe neurons evokes more 5-HT release in the brain of condition knockout (cKO) mice with Pten-deficient 5-HT neurons. In addition, the 5-HT neurons remain normal electrophysiological properties but have increased excitatory synaptic inputs. Single-cell RNA sequencing revealed gene transcript alterations that may underlay morphological and functional changes in Pten-deficient 5-HT neurons. Finally, Pten cKO mice and wild-type mice treated with systemic application of PTEN inhibitor display reduced depression-like behaviors. Thus, PTEN is an intrinsic regulator of 5-HT neuron activity, representing a novel therapeutic strategy for producing antidepressant action. |
