| First Author | Ren Z | Year | 2015 |
| Journal | Neuropharmacology | Volume | 88 |
| Pages | 171-9 | PubMed ID | 25107590 |
| Mgi Jnum | J:319097 | Mgi Id | MGI:6862707 |
| Doi | 10.1016/j.neuropharm.2014.07.019 | Citation | Ren Z, et al. (2015) Defects in dendrite and spine maturation and synaptogenesis associated with an anxious-depressive-like phenotype of GABAA receptor-deficient mice. Neuropharmacology 88:171-9 |
| abstractText | Mice that were rendered heterozygous for the gamma2 subunit of GABAA receptors (gamma2(+/-) mice) have been characterized extensively as a model for major depressive disorder. The phenotype of these mice includes behavior indicative of heightened anxiety, despair, and anhedonia, as well as defects in hippocampus-dependent pattern separation, HPA axis hyperactivity and increased responsiveness to antidepressant drugs. The gamma2(+/-) model thereby provides strong support for the GABAergic deficit hypothesis of major depressive disorder. Here we show that gamma2(+/-) mice additionally exhibit specific defects in late stage survival of adult-born hippocampal granule cells, including reduced complexity of dendritic arbors and impaired maturation of synaptic spines. Moreover, cortical gamma2(+/-) neurons cultured in vitro show marked deficits in GABAergic innervation selectively when grown under competitive conditions that may mimic the environment of adult-born hippocampal granule cells. Finally, brain extracts of gamma2(+/-) mice show a numerical but insignificant trend (p = 0.06) for transiently reduced expression of brain derived neurotrophic factor (BDNF) at three weeks of age, which might contribute to the previously reported developmental origin of the behavioral phenotype of gamma2(+/-) mice. The data indicate increasing congruence of the GABAergic, glutamatergic, stress-based and neurotrophic deficit hypotheses of major depressive disorder. |
