Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory

Hung, Hui Chi; Hsiao, Ya Hsin; Gean, Po Wu

doi:10.1016/j.euroneuro.2015.07.005

Cited by 15 publications

(9 citation statements)

References 50 publications

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“…Considering that extinction is new learning (Quirk and Mueller, ), formation of extinction memory was most probably compromised, causing transgenic animals to be unable to learn that the aversive stimulus from acquisition was no longer present. Thus, our result is in agreement with previous studies in mouse models with reduced neurogenesis, which also showed impaired fear extinction (Deng et al, ; Pan et al, ; Hung et al, ). This might be because transgenics were unable to store the correct emotional memory presented during acquisition trial, so that in the following expositions to the context, the overreaction was due to inadequate emotional memory consolidation.…”

Section: Discussionsupporting

confidence: 94%

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

et al. 2016

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It is well known that adult neurogenesis occurs in two distinct regions, the subgranular zone of the dentate gyrus and the subventricular zone along the walls of the lateral ventricles. Until now, the contribution of these newly born neurons to behavior and cognition is still uncertain. The current study tested the functional impacts of diminished hippocampal neurogenesis on emotional and cognitive functions in transgenic Gfap-tk mice. Our results showed that anxiety-related behavior evaluated both in the elevated plus maze as well as in the open field, social interaction in the sociability test, and spatial working memory in the spontaneous alternation test were not affected. On the other hand, recognition and emotional memory in the object recognition test and contextual fear conditioning, and hippocampal long-term potentiation were impaired in transgenic mice. Furthermore, we evaluated whether environmental enrichment together with physical exercise could improve or even restore the level of adult neurogenesis, as well as the behavioral functions. Our results clearly demonstrated that environmental enrichment together with physical exercise successfully elevated the overall number of progenitor cells and young neurons in the dentate gyrus of transgenic mice. Furthermore, it led to a significant improvement in object recognition memory and contextual fear conditioning, and reverted impairments in hippocampal long-term potentiation. Thus, our results confirm the importance of adult neurogenesis for learning and memory processes and for hippocampal circuitry in general. Environmental enrichment and physical exercise beneficially influenced adult neurogenesis after it had been disrupted and most importantly recovered cognitive functions and long-term potentiation. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 94%

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

et al. 2016

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“…Plasmids carrying specific SHH gene short-hairpin RNA (shRNA) and negative control (NC) shRNA (Table 1) were constructed by Sangon Biotech, Shanghai, China, with the sequences as previously published [29]. Each HCC cell line was divided into three groups: the parental group, the NC group, HCC cells transfected with NC plasmid, and the sh SHH group, HCC cells transfected shRNA plasmid.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of the Sonic Hedgehog (SHH) Gene Inhibits Proliferation of Hep3B and SMMC-7721 Hepatocellular Carcinoma Cells via the PI3K/Akt/PCK1 Signaling Pathway

Chen

Zhu

2019

Med Sci Monit

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Background The PCK1 gene encodes phosphoenolpyruvate carboxykinase (PEPCK), which has been shown have a role in metabolic events in hepatocellular carcinoma (HCC). This study aimed to investigate the role of the SHH gene and its encoded protein, sonic hedgehog (SHH), in two human hepatocellular carcinoma (HCC) cell lines. Material/Methods The human HCC cell lines Hep3B and SMMC-7721 were cultured. Cells were transfected with plasmids carrying specific SHH gene short-hairpin RNA (shRNA) and negative control (NC) shRNA. The effects of knockdown of expression levels of the SHH gene were studied on cell survival, cell apoptosis, the cell cycle, gluconeogenesis, and the expression of PCK1 . Anchorage-independent growth, a characteristic of transformed cells, was detected by the colony formation assay. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were performed 24 h after transfection. Results Knockdown of expression levels of the SHH gene reduced cell proliferation and growth of HCC cells and induced cell apoptosis and G1 cell cycle arrest in both HCC cell lines. Knockdown of the SHH gene decreased the levels of glycolysis products and increased the production of glucose and reduced the phosphorylation of PI3K and Akt but induced the expression of PCK1 . Conclusions Knockdown of the SHH gene reduced cell survival of HCC cells by increasing apoptosis, reducing cell proliferation, inducing G1 cell cycle arrest, and restoring gluconeogenesis, and was associated with the inhibition of the PI3K/Akt axis and induced the expression of PCK1 .

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“…c1507) were purchased from Applygen Technologies Inc. (Beijing, China). A specific SHH -targeted shRNA (5′-CCCGACATCATATTTAAGGAT-3′) and control shRNA (5′-GCTGTTGGACAGCGAGACCAT-3′) were constructed by Wanlei Life Sciences (Shenyang, China) in accordance with a previous study ( 11 ). The human RB WERI-Rb-1 cell line was obtained from Wanlei Life Sciences and cultured in RPMI-1640 medium (cat.…”

Section: Methodsmentioning

confidence: 99%

Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway

Song

Ying

2017

Oncology Letters

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Retinoblastoma (RB) is the most common type of malignant intraocular cancer in teenagers. One of the proteins abnormally expressed during oncogenesis of RB is sonic hedgehog (SHH), which possesses the capability to selectively activate transcription factors of different genes. However, the detailed function of SHH in RB remains unknown. Thus, the present study sought to investigate the role of SHH in the development of RB. The human RB WERI-Rb-1 cell line was used as an in vitro model for the knockdown of SHH by a specific short hairpin RNA (shRNA). To assess the effect of SHH inhibition on cell growth and apoptosis, cell viability, colony formation and flow cytometry assays were conducted. WERI-Rb-1 cells transfected with an shRNA targeting SHH were treated with the phosphoinositide-3 kinase (PI3K)/Akt agonist insulin-like growth factor 1 (IGF-1) to investigate the possible mechanism by which SHH promotes RB. The present results revealed that the silencing of SHH induced G1 cell-cycle arrest and apoptosis in WERI-Rb-1 cells and led to a decrease in cell viability, indicating that SHH has a critical role in the determination of RB cell survival. Moreover, according to the results of the IGF-1 assays, suppression of PI3K/Akt was a prerequisite for SHH inhibition, illuminating its potential role in the treatment of RB. The findings outlined in the present study elucidate a clear link between SHH and the PI3K/Akt pathway in RB cell survival, which could provide valuable inspiration for the advancement of therapies against RB.

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Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory

Cited by 15 publications

References 50 publications

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

Knockdown of the Sonic Hedgehog (SHH) Gene Inhibits Proliferation of Hep3B and SMMC-7721 Hepatocellular Carcinoma Cells via the PI3K/Akt/PCK1 Signaling Pathway

Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway

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