Wnt Signaling Is Required for Long-Term Memory Formation

Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

doi:10.1016/j.celrep.2013.08.007

Cited by 32 publications

(29 citation statements)

References 32 publications

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“…Presumably, strict balance in protein synthesis and degradation should be preserved for maintenance of long-term memory. Enrichment of Wnt pathway is also compatible with previous findings of the involvement of this signaling in regulation of late phase LTP and LTM (120,121). Enhancement of metabolic activity introduces strong demand in the energetic resources, which were found to be supplied by up-regulation of proteins involved in glycolysis and the ATP biosynthesis machinery (Fig.…”

Section: Discussionsupporting

confidence: 77%

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Borovok

Nesher

Levin

et al. 2016

Molecular & Cellular Proteomics

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Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phasecurbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) Long-term synaptic plasticity is considered a cellular correlate of long-term memory (LTM) 1 . Contemporary understanding of memory formation is based on the initiation and maintenance of long-term synaptic plasticity (1-4), for which de novo protein synthesis is a vital requirement. De novo protein synthesis itself is secondary to activity-dependent changes in synapses that occur during learning processes. These activity changes trigger post-translational modifications of proteins initiating and sustaining multiple signal transduction pathways. In turn, these signaling pathways regulate changes in synaptic strength and connectivity by governing gene expression and protein translation (5-13). Depending on time elapsed since triggering of long-term synaptic plasticity, protein synthesis may be limited to the dendrites directly involved in the plasticity processes (14 -18). Multiple synaptic From the ‡Department

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Section: Discussionsupporting

confidence: 77%

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Borovok

Nesher

Levin

et al. 2016

Molecular & Cellular Proteomics

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“…Wnt/β-catenin pathway plays an important role in the hippocampal neurogenesis, self-renewal of NSC and cognitive function [55,83,84]. Activated Wnt signaling is a major initiation and promotion factor of neurogenesis because of its ability to selectively trigger a panel of neuronal-associated gene expression for NSC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

et al. 2015

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Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor, utilized for production of consumer products, and exerts adverse effects on the developing nervous system. Recently, we found that BPA impairs the finely tuned dynamic processes of neurogenesis (generation of new neurons) in the hippocampus of the developing rat brain. Curcumin is a natural polyphenolic compound, which provides neuroprotection against various environmental neurotoxicants and in the cellular and animal models of neurodegenerative disorders. Here, we have assessed the neuroprotective efficacy of curcumin against BPA-mediated reduced neurogenesis and the underlying cellular and molecular mechanism(s). Both in vitro and in vivo studies showed that curcumin protects against BPA-induced hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural stem cells (NSC) proliferation and neuronal differentiation and enhanced neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity involved activation of the Wnt/β-catenin signaling pathway, which was confirmed by the use of Wnt specific activators (LiCl and GSK-3β siRNA) and inhibitor (Dkk-1). BPA-mediated increased β-catenin phosphorylation, decreased GSK-3β levels, and β-catenin nuclear translocation were significantly reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with improved learning and memory in BPA-treated rats. Overall, our results conclude that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis via activation of the Wnt/β-catenin signaling pathway.

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“…We found four Wnt signaling pathway genes are associated with variation in re-mating. Though the Wnt signaling pathway has not yet been implicated in the regulation of female post-mating behavior, Wnt signaling is necessary for female fertility in mammals (Boyer et al 2010), and for long-term memory formation in Drosophila (Tan et al 2013). Given that the GWAS will identify genes that could have an impact during development, and on any tissue, it is not unexpected that we would find different genes than identified in our gene expression analyses.…”

Section: Discussionmentioning

confidence: 83%

TheDrosophilaPost-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions

Newell

Ray

Dalton

et al. 2020

G3 Genes|Genomes|Genetics

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Examining cross-tissue interactions is important for understanding physiology and homeostasis. In animals, the female gonad produces signaling molecules that act distally. We examine gene expression in Drosophila melanogaster female head tissues in 1) virgins without a germline compared to virgins with a germline, 2) post-mated females with and without a germline compared to virgins, and 3) post-mated females mated to males with and without a germline compared to virgins. In virgins, the absence of a female germline results in expression changes in genes with known roles in nutrient homeostasis. At one-and three-day(s) post-mating, genes that change expression are enriched with those that function in metabolic pathways, in all conditions. We systematically examine female post-mating impacts on sleep, food preference and re-mating, in the strains and time points used for gene expression analyses and compare to published studies. We show that post-mating, gene expression changes vary by strain, prompting us to examine variation in female re-mating. We perform a genome-wide association study that identifies several DNA polymorphisms, including four in/near Wnt signaling pathway genes. Together, these data reveal how gene expression and behavior in females are influenced by cross-tissue interactions, by examining the impact of mating, fertility, and genotype.

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Wnt Signaling Is Required for Long-Term Memory Formation

Cited by 32 publications

References 32 publications

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

TheDrosophilaPost-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions

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