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.

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Shh pathway play vital role in oligodendrocytes differentiation and Nkx2.2 transcription factor is essential for o ligodendrocytes differentiation and maturation. Intriguingly, down regulation of Nkx2.2 transcription factor with aberrant Shh signaling pathway is reported in glioma samples. So here suggest that Nkx2.2 expression pattern could be used as a potential biomarker for the early diagnosis of glioma.

Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Methods Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. Results A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium‐treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium‐treated rats.