Increased hippocampal neurogenesis and accelerated response to antidepressants in mice with specific deletion of CREB in the hippocampus: role of cAMP response-element modulator τ.

The transcription factor cAMP response element-binding protein (CREB) has been implicated in the pathophysiology of depression as well as in the efficacy of antidepressant treatment. However, altering CREB levels appears to have differing effects on anxiety- and depression-related behaviors, depending on which brain region is examined. Furthermore, many manipulations of CREB lead to corresponding changes in other CREB family proteins, and the impact of these changes has been largely ignored.

Selective deletion of a cell cycle checkpoint kinase (ATR) reduces neurogenesis and alters responses in rodent models of behavioral affect.

Hippocampal function has been implicated in mood and anxiety disorders, as well as in the response to antidepressant (AD) treatment. However, the significance of new neurons in the therapeutic mechanism of ADs remains unclear. In this study, the proliferation of new neurons was inhibited through conditional deletion of ataxia telangeictasia-mutated and rad-3 related (ATR), a cell cycle checkpoint kinase, and cellular and behavioral outcomes following AD exposure were evaluated.