The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors

Zhou, Wuding; Xu, Ning; Kong, Ling-Dong; Sc, Sun; Xu, Xiaohui; Jia, M-Z; Wang, Y; Chen, Zhong

doi:10.1038/tp.2016.122

Cited by 47 publications

(44 citation statements)

References 68 publications

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“…Specifically, the levels of two key proteins in Wnt4 signaling, WNT4 and Dishevelled 2 (DVL2) were increased in F1 brain tissue (Dai et al, 2017). Disruption of Wnt signaling is seen in bipolar disorder and major depressive disorder (Voleti & Duman, 2012), and knockdown of Wnt signaling genes results in depressive-like phenotypes (Zhou et al, 2016). Alternatively, anti-depressants activate Wnt signaling (Okamoto et al, 2010).…”

Section: Nicotinementioning

confidence: 99%

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Goldberg

Gould

2018

Eur J of Neuroscience

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Addictions are highly heritable disorders, with heritability estimates ranging from 39% to 72%. Multiple studies suggest a link between paternal drug abuse and addiction in their children. However, patterns of inheritance cannot be explained purely by Mendelian genetic mechanisms. Exposure to drugs of abuse results in epigenetic changes that may be passed on through the germline. This mechanism of epigenetic transgenerational inheritance may provide a link between paternal drug exposure and addiction susceptibility in the offspring. Recent studies have begun to investigate the effect of paternal drug exposure on behavioral and neurobiological phenotypes in offspring of drug-exposed fathers in rodent models. This review aims to discuss behavioral and neural effects of paternal exposure to alcohol, cocaine, opioids, and nicotine. Although a special focus will be on addiction-relevant behaviors, additional behavioral effects including cognition, anxiety, and depressive-like behaviors will be discussed.

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Section: Nicotinementioning

confidence: 99%

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Goldberg

Gould

2018

Eur J of Neuroscience

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“…SPT was conducted as previously described [9]. Briefly, after CUMS procedure, mice were deprived of water starting from 8:00 p.m. From the second day, mice were accustomed 1% sucrose solution for 3 days (1 hour per day, between 8:00 a.m. and 9:00 a.m.).…”

Section: Sptmentioning

confidence: 99%

“…Previous studies have shown that the downstream pathway of Wnt/β-catenin signaling is associated with depression [8]. In addition, Wnt2 and Wnt3 have been shown to have antidepressant effects [9]. However, the mechanism of Wnt in depression is not clear.…”

Section: Introductionmentioning

confidence: 99%

MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons

et al. 2018

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Objective: The aim of this study was to investigate the mechanism of miR-221 in depression. Methods: The molecules expressions were measured by qRT-PCR and western blot. The sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST) were used to detect depressive-like symptoms. MTT assay and flow cytometric was used to measure the proliferation and apoptosis of hippocampal neuronal. Results: MiR-221 expression in the cerebrospinal fluid and serum of major depressive disorder patients and the hippocampus of chronic unpredictable mild stress (CUMS) mice were increased, while the expression of Wnt2, p-CREB and BDNF were decreased. Additionally, silence of miR-221 increased sucrose preference of CUMS mice and shortened the immobility time of CUMS mice in SPT and FST. MiR-221 could targeted regulate Wnt2, and knockdown of Wnt2 reversed the effect of miR-221 inhibitor on the proliferation and apoptosis of hippocampal neurons and countered the promoting effect of miR-221 inhibitor on the expression of Wnt2, p-CREB and BDNF. Conclusion: MiR-221 could promote the development of depression by regulating Wnt2/CREB/ BDNF axis. ARTICLE HISTORY

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“…Given the described changes in the Wnt signaling pathway, a follow-up question would be whether pharmacological regulation of Wnt signaling represents an important and/or plausible treatment strategy for PMS and ASD. Notably, several medications have been shown to modulate Wnt signaling, including methylphenidates [92], selective serotonin reuptake inhibitors (SSRIs) [93] and some antipsychotic medications [89, 94]. For example, long-term administration of methylphenidate in mice has been shown to modulate key components of the Wnt signaling pathway, including Akt and GSK3 [92].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, SSRI treatment ( e.g. fluoxetine) has been shown to boost Wnt signaling, specifically Wnt2 and Wnt3 in two different mouse studies [93, 95]. Further, two additional reports have also demonstrated that the antipsychotic medication haloperidol promotes Wnt signalling, including WNT5A and β-catenin expression [96] as well as the phosphorylation of Akt [94].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan McDermid syndrome and autism

Breen

Browne

Hoffman

et al. 2019

Preprint

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28Background: Phelan-McDermid syndrome (PMS) is a rare genetic disorder with high risk of 29 autism spectrum disorder (ASD), intellectual disability and language delay, and is caused by 30 22q13.3 deletions or mutations in the SHANK3 gene. To date, the molecular and pathway changes 31 resulting from SHANK3 haploinsufficiency in PMS remain poorly understood. Uncovering these 32 mechanisms is critical for understanding pathobiology of PMS and, ultimately, for the 33 development of new therapeutic interventions. 34 35 Methods: We developed human induced pluripotent stem cell (hiPSC)-based models of PMS by 36reprogramming peripheral blood samples from individuals with PMS (n=7) and their unaffected 37 siblings (n=6). For each participant, up to three hiPSC clones were generated and differentiated 38 into induced neural progenitor cells (iNPCs; n=32) and induced forebrain neurons (iNeurons; 39 n=42). Genome-wide RNA-sequencing was applied to explore transcriptional differences between 40 PMS probands and unaffected siblings. 41 42 Results: Transcriptome analyses identified 391 differentially expressed genes (DEGs) in iNPCs 43 and 82 DEGs in iNeurons, when comparing cells from PMS probands and unaffected siblings 44 (FDR <5%). Genes under-expressed in PMS were implicated in Wnt signaling, embryonic 45 development and protein translation, while over-expressed genes were enriched for pre-and post-46 synaptic density genes, regulation of synaptic plasticity, and G-protein-gated potassium channel 47 activity. Gene co-expression network analysis identified two modules in iNeurons that were over-48 expressed in PMS, implicating postsynaptic signaling and GDP binding, and both modules 49 harbored a significant enrichment of genetic risk loci for developmental delay and intellectual 50 3 disability. Finally, PMS-associated genes were integrated with other ASD iPSC transcriptome 51 findings and several points of convergence were identified, indicating altered Wnt signaling, 52 extracellular matrix and glutamatergic synapses. 53 54 Limitations: Given the rarity of the condition, we could not carry out experimental validation in 55 independent biological samples. In addition, functional and morphological phenotypes caused by 56 loss of SHANK3 were not characterized here. 57 58 Conclusions: This is the largest human neural sample analyzed in PMS. Genome-wide RNA-59 sequencing in hiPSC-derived neural cells from individuals with PMS revealed both shared and 60 distinct transcriptional signatures across iNPCs and iNeurons, including many genes implicated in 61 risk for ASD, as well as specific neurobiological pathways, including the Wnt pathway. 62 63 64 Phelan-McDermid syndrome (PMS) is one of the most penetrant and more common single-locus 66 causes of ASD, accounting for ca. 1% of ASD diagnoses [1-3]. PMS is caused by heterozygous 67 22q13.3 deletions or mutations leading to haploinsufficiency of the SHANK3 gene [2, 4-6]. 68 Clinical manifestations of PMS include ASD, global developmental delay, severe to profound 69 intellectual ...

show abstract

The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors

Cited by 47 publications

References 68 publications

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons

Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan McDermid syndrome and autism

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