跳转至内容
Merck
  • TrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response.

TrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response.

Nature communications (2017-11-23)
Zhenzhong Ma, Tong Zang, Shari G Birnbaum, Zilai Wang, Jane E Johnson, Chun-Li Zhang, Luis F Parada
摘要

Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at the cellular level to sustain this anti-depressive function for prolonged periods remains unclear. Here we report that ketamine accelerates differentiation of doublecortin-positive adult hippocampal neural progenitors into functionally mature neurons. This process requires TrkB-dependent ERK pathway activation. Genetic ablation of TrkB in neural stem/progenitor cells, or pharmacologic disruption of ERK signaling, or inhibition of adult neurogenesis, each blocks the ketamine-induced behavioral responses. Conversely, enhanced ERK activity via Nf1 gene deletion extends the response and rescues both neurogenic and behavioral deficits in mice lacking TrkB. Thus, TrkB-dependent neuronal differentiation is involved in the sustained antidepressant effects of ketamine.

材料
货号
品牌
产品描述

Sigma-Aldrich
抗NeuN抗体(兔), from rabbit, purified by affinity chromatography
Sigma-Aldrich
生物胞素, ≥98% (TLC)
Sigma-Aldrich
SL327, ≥98% (HPLC), Mixture of E & Z isomers, solid