Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Neurosci Lett. 2019 Jun 21;704:67-72. doi: 10.1016/j.neulet.2019.03.052. Epub 2019 Mar 30.
Chronic lithium treatment stimulates adult hippocampal neurogenesis, but whether increased neurogenesis contributes to its therapeutic mechanism remains unclear. We use a genetic model of neural progenitor cell (NPC) ablation to test whether a lithium-sensitive behavior requires hippocampal neurogenesis. NPC-ablated mice were treated with lithium and assessed in the forced swim test (FST). Lithium reduced time immobile in the FST in NPC-ablated and control mice but had no effect on activity in the open field, a control for the locomotion-based FST. These findings show that hippocampal NPCs that proliferate in response to chronic lithium are not necessary for the behavioral response to lithium in the FST. We further show that 4-6 week old immature hippocampal neurons are not required for this response. These data suggest that increased hippocampal neurogenesis does not contribute to the response to lithium in the forced swim test and may not be an essential component of its therapeutic mechanism.
慢性锂处理刺激成年海马神经发生，但增加的神经发生是否有助于其治疗机制尚不清楚。我们使用神经祖细胞 (NPC) 消融的遗传模型来测试锂敏感行为是否需要海马神经发生。对 NPC 消融的小鼠进行锂处理，并在强迫游泳试验 (FST) 中进行评估。锂可减少 NPC 消融和对照小鼠在 FST 中的不动时间，但对开放场中的活动没有影响，这是 FST 中基于运动的对照。这些发现表明，对慢性锂反应而增殖的海马 NPC 对于 FST 中对锂的行为反应不是必需的。我们进一步表明，4-6 周龄的不成熟海马神经元不需要这种反应。这些数据表明，增加的海马神经发生不会导致强迫游泳试验中对锂的反应，也可能不是其治疗机制的必要组成部分。
