Disruption of Sonic Hedgehog Signaling Accelerates Age-Related Neurogenesis Decline and Abolishes Stroke-Induced Neurogenesis and Leads to Increased Anxiety Behavior in Stroke Mice

Wang, Jiapeng; Ware, Kierra; Bedolla, Alicia; Allgire, Emily; Turcato, Flavia; Weed, Maxwell; Sah, Renu; Luo, Yu

doi:10.1007/s12975-022-00994-w

Cited by 14 publications

(8 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another well-known effect of Shh signaling is the maintenance of adult neural stem cells. We and others have reported that abolishing Shh signaling in the mGFAPcre mouse line results in decreased adult neurogenesis in both the SVZ and SGZ, and our recent study shows that Shh KO further accelerates the age-related decline in adult neurogenesis and contributes to increased anxiety in mGFAP-smo cKO mice ( Wang et al., 2022 ). As SN DA neuron projections have been previously reported to regulate SVZ NSCs at least partially through the release of dopamine ( Garcia-Garrote et al., 2021 ; Hoglinger et al., 2004 ), we examined whether midbrain DA neuron projections could potentially provide SHH ligand to the SVZ NSCs in order to maintain their homeostasis.…”

Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

“…It has been reported by others and by our group that Shh signaling in postnatal neural stem cells (NSCs) is critical for maintaining adult neurogenesis ( Lai et al., 2003 ; Petrova et al., 2013 ; Wang et al., 2022 ). We have recently reported that the deletion of the Shh receptor Smoothened (SMO) in Glial fibrillary acidic protein (GFAP) positive NSCs at the perinatal stage leads to premature aging-related decline of adult neurogenesis ( Wang et al., 2022 ). DA neuron projections have been described at the SVZ region where the adult neural stem cells reside and have been suggested to regulate SVZ neurogenesis through the release of factors such as dopamine ( Garcia-Garrote et al., 2021 ; Hoglinger et al., 2004 ).…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

Turcato¹,

Wegman²,

Lü³

et al. 2022

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

Turcato¹,

Wegman²,

Lü³

et al. 2022

iScience

View full text Add to dashboard Cite

“…Intriguingly, we previously reported that HMF exposure increased ROS content in the whole hippocampus by Frontiers in Physics frontiersin.org modulating the key genes expression of the oxidative stress and antioxidant defense, except the subgranular zone of dentate gyrus [19], which suggests that oxidative stress in the hippocampus may contribute to the anxiety-like behavior found in this study. Besides, other studies suggested that decreased neurogenesis or ablation of neurogenesis usually led to an increased anxiety-like behavior [59,60]. And the recovery of anxiety also requires the inevitable involvement of neurogenesis [61-63].…”

Section: Discussionmentioning

confidence: 99%

Effects of hypomagnetic field on adult hippocampal neurogenic niche and neurogenesis in mice

Luo

Zhan²,

Yang³

et al. 2022

Front. Phys.

View full text Add to dashboard Cite

The elimination of geomagnetic field (GMF), also called hypomagnetic field (HMF), is one of the major environmental hazards faced by deep-space astronauts and the workers in magnetically shielded rooms on Earth. We previously reported that long-term HMF exposure impaired adult hippocampal neurogenesis (AHN) and cognition by reducing endogenous reactive oxygen species (ROS) levels in adult neural stem cells (aNSCs). In addition to the aNSCs themselves, adult neurogenesis is also regulated by the local environment, i.e., the neurogenic niche. Neurogenic niche is mainly composed of astrocyte, microglia, and vascular system. However, whether the HMF exposure affects the neurogenic niche in hippocampus remains unknown. In this study, we investigated the effects of the HMF exposure on the neurogenic niche and adult neurogenesis in hippocampus, as well as the cognitive function in mice. The HMF is simulated by using the newly upgraded double-wrapped coils, different with our previous coils, which are capable of providing a very low-strength static magnetic field and identical electromagnetic field background between the HMF group and the GMF group. Here, we for the first time clearly revealed that 8-week HMF exposure significantly induced microglia activation and increased the number of astrocytes in hippocampal dentate gyrus (DG), suggesting the abnormalities in the neurogenic niche. Meanwhile, 8-week HMF exposure also markedly reduced proliferation and differentiation of aNSCs in the DG, and impaired the cognitive behavior of mice, consistent with our previous findings. In addition, we also found that 8-week HMF exposure significantly induced anxiety-like behaviors of mice. In summary, this study indicates that 8-week HMF exposure induces the neurogenic niche abnormalities, contributing to the AHN impairments, thus leads to the cognitive dysfunction and anxiety-like behaviors in mice.

show abstract

“…In contrast, the Hh pathway is predominantly insufficiently active or even quiescent in mature organisms. As necessary, under certain conditions, it would be activated, such as wound healing and tissue recovery [21,22] in bone [23,24], intervertebral disc [25], heart, nerves [26][27][28][29], skin [30], muscle [31], and gastrointestinal mucosa [32,33]. However, componential activation of the Hh signaling pathway is responsible for the formation and progression of diverse cancer types, i.e., basal cell carcinoma (BCC) [34,35].…”

Section: Introductionmentioning

confidence: 99%

The role of Hedgehog and Notch signaling pathway in cancer

Xia

Yang

et al. 2022

Mol Biomed

View full text Add to dashboard Cite

Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.

show abstract

Disruption of Sonic Hedgehog Signaling Accelerates Age-Related Neurogenesis Decline and Abolishes Stroke-Induced Neurogenesis and Leads to Increased Anxiety Behavior in Stroke Mice

Cited by 14 publications

References 51 publications

Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

Effects of hypomagnetic field on adult hippocampal neurogenic niche and neurogenesis in mice

The role of Hedgehog and Notch signaling pathway in cancer

Contact Info

Product

Resources

About