Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh, India.
Department of Biochemistry and Genetics, University of Navarra, Faculty of Sciences, Pamplona, Spain.
J Neurosci Res. 2018 Jan;96(1):53-62. doi: 10.1002/jnr.24104. Epub 2017 Jun 20.
There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF. Antidepressants are known to upregulate the adult hippocampal neurogenesis to treat depression. Shh plays an important role in adult hippocampal neurogenesis, and its downstream signaling components regulate the synthesis of Wnt proteins. Moreover, the expression of Gli1 and Smo is downregulated in depression. BDNF and Wnt signaling are also regulated by various available antidepressants, so there is the possibility that Shh may be involved in the pathophysiology of depression. Therefore, the crosstalk between the Shh, Wnt, and BDNF signaling pathways is being discussed to identify the potential targets. Specifically, the potential role of the Shh signaling pathway in depression is explored as a new target for better therapies for depression.
有各种理论来解释抑郁症的病理生理学，并支持其诊断和治疗。单胺类、脑源性神经营养因子（BDNF）和 Wnt 信号的作用研究得很好，但 Sonic Hedgehog（Shh）信号及其下游转录因子 Gli1 在抑郁症中的研究并不充分。Shh 信号在胚胎发育和成年海马神经发生中起着基本作用，也参与了癌症的生长。在本文中，我们总结了 Shh 信号通路在抑郁症中的证据，以及 Shh 与 Wnt 和 BDNF 之间的潜在串扰。已知抗抑郁药可上调成年海马神经发生来治疗抑郁症。Shh 在成年海马神经发生中起着重要作用，其下游信号成分调节 Wnt 蛋白的合成。此外，Gli1 和 Smo 的表达在抑郁症中下调。BDNF 和 Wnt 信号也受各种可用的抗抑郁药调节，因此 Shh 可能参与了抑郁症的病理生理学。因此，正在讨论 Shh、Wnt 和 BDNF 信号通路之间的串扰，以确定潜在的靶点。具体来说，探讨了 Shh 信号通路在抑郁症中的潜在作用，作为治疗抑郁症的更好疗法的新靶点。
