Improved memory and reduced anxiety in δ-catenin transgenic mice

Ryu, Taeyong; Park, Hyung Joon; Kim, Hangun; Cho, Young-Chang; Kim, Byeong C.; Jo, Jihoon; Seo, Young-Woo; Choi, Wonseok; Kim, Kwonseop

doi:10.1016/j.expneurol.2019.04.006

Cited by 12 publications

(10 citation statements)

References 62 publications

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“…Interestingly, GWAS studies have also shown SNPs on deltacatenin that are associated with anxiety and depression (Nivard et al, 2014). Recent studies in delta-catenin transgenic mice have confirmed that higher levels of delta-catenin are correlated with reduced anxiety and improved memory (Ryu et al, 2019).…”

Section: Pathological Associations Of Delta-catenin Neurological Path...mentioning

confidence: 99%

Delta-Catenin as a Modulator of Rho GTPases in Neurons

Donta

Srivastava

McCrea

2022

Front. Cell. Neurosci.

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Small Rho GTPases are molecular switches that are involved in multiple processes including regulation of the actin cytoskeleton. These GTPases are activated (turned on) and inactivated (turned off) through various upstream effector molecules to carry out many cellular functions. One such upstream modulator of small Rho GTPase activity is delta-catenin, which is a protein in the p120-catenin subfamily that is enriched in the central nervous system. Delta-catenin affects small GTPase activity to assist in the developmental formation of dendrites and dendritic spines and to maintain them once they mature. As the dendritic arbor and spine density are crucial for synapse formation and plasticity, delta-catenin’s ability to modulate small Rho GTPases is necessary for proper learning and memory. Accordingly, the misregulation of delta-catenin and small Rho GTPases has been implicated in several neurological and non-neurological pathologies. While links between delta-catenin and small Rho GTPases have yet to be studied in many contexts, known associations include some cancers, Alzheimer’s disease (AD), Cri-du-chat syndrome, and autism spectrum disorder (ASD). Drawing from established studies and recent discoveries, this review explores how delta-catenin modulates small Rho GTPase activity. Future studies will likely elucidate how PDZ proteins that bind delta-catenin further influence small Rho GTPases, how delta-catenin may affect small GTPase activity at adherens junctions when bound to N-cadherin, mechanisms behind delta-catenin’s ability to modulate Rac1 and Cdc42, and delta-catenin’s ability to modulate small Rho GTPases in the context of diseases, such as cancer and AD.

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Section: Pathological Associations Of Delta-catenin Neurological Path...mentioning

confidence: 99%

Delta-Catenin as a Modulator of Rho GTPases in Neurons

Donta

Srivastava

McCrea

2022

Front. Cell. Neurosci.

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“…This encodes a protein regulating the dendritic spine and synapse development through rho-family GTPases and cadherins 44 . The overexpression of CTNND1 has been linked to improved memory and reduced anxiety in mice 45 . The CNNM2 gene, encoding a cyclin protein involved in Mg 2+ transport, has been associated with impaired neuronal development and epilepsy 46 .…”

Section: Discussionmentioning

confidence: 99%

“…The overexpression of CTNND1 has been linked to improved memory and reduced anxiety in mice 45 . The CNNM2 gene, encoding a cyclin protein involved in Mg 2+ transport, has been associated with impaired neuronal development and epilepsy 46 .…”

Section: Discussionmentioning

confidence: 99%

Gene Discovery and Biological Insights into Anxiety Disorders from a Multi-Ancestry Genome-wide Association Study of >1.2 Million Participants

Friligkou,

Løkhammer,

Cabrera-Mendoza

et al. 2024

Preprint

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We leveraged information from more than 1.2 million participants to investigate the genetics of anxiety disorders across five continental ancestral groups. Ancestry-specific and cross-ancestry genome-wide association studies identified 51 anxiety-associated loci, 39 of which are novel. Additionally, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, Admixed-American, and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, the cerebral cortex, the cerebellum, the metencephalon, the entorhinal cortex, and the brain stem. Transcriptome- and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. We also observed global and local genetic correlations with depression, schizophrenia, and bipolar disorder and putative causal relationships with several physical health conditions. Overall, this study expands the knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.

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“…Indeed, δ2-catenin plays a role in synaptic forward junctions, and it has been to induce morphological changes in the branching and/or prolongation of postsynaptic dendrites based on measurements of synaptic activity [59]. Overexpression of δ2-catenin has also been reported to improve memory [60]. TMEM163, or synaptic vesicle 31, is part of several cellular compartments, including synaptic-like microvesicles, which overlap with zinc enrichment in presynaptic vesicles [61].…”

Section: Hippocampal Proteomementioning

confidence: 99%

The Human Hippocampus in Parkinson’s Disease: An Integrative Stereological and Proteomic Study

Villar‐Conde

Astillero‐Lopez

González-Rodríguez

et al. 2021

JPD

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Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disease that is pathologically described as a six-stage α-synucleinopathy. In stage 4, α-synuclein reaches the hippocampus, inducing cognitive deficits, from which it progresses to the isocortex, leading to dementia. Among hippocampal fields, cornu ammonis 2 is particularly affected by this α-synucleinopathy and critical for cognitive decline. Volumetric studies using magnetic resonance imaging have produced controversial results, with only some reporting volume loss, whereas stereological data obtained using nonspecific markers do not reveal volume changes, neural or glial loss. Proteomic analysis has not been carried out in the hippocampus of patients with PD. Objective: This study aims to explain hippocampal changes in patients with PD at the cellular and proteomic levels. Methods: α-Synuclein inclusions, volume and neural (NeuN), microglial (Iba-1) and astroglial (GFAP) populations were stereologically analyzed. SWATH-MS quantitative proteomic analysis was also conducted. Results: Area fraction fractionator probe revealed a higher area fraction α-synucleinopathy in cornu ammonis 2. No volume change, neurodegeneration, microgliosis or astrogliosis was detected. Proteomic analysis identified 1,634 proteins, of which 83 were particularly useful for defining differences among PD and non-PD groups. Among them, upregulated (PHYIP, CTND2, AHSA1 and SNTA1) and downregulated (TM163, REEP2 and CSKI1) proteins were related to synaptic structures in the diseased hippocampus. Conclusion: The distribution of α-synuclein in the hippocampus is not associated with volumetric, neural or glial changes. Proteomic analysis, however, reveals a series of changes in proteins associated with synaptic structures, suggesting that hippocampal changes occur at the synapse level during PD.

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Improved memory and reduced anxiety in δ-catenin transgenic mice

Cited by 12 publications

References 62 publications

Delta-Catenin as a Modulator of Rho GTPases in Neurons

Delta-Catenin as a Modulator of Rho GTPases in Neurons

Gene Discovery and Biological Insights into Anxiety Disorders from a Multi-Ancestry Genome-wide Association Study of >1.2 Million Participants

The Human Hippocampus in Parkinson’s Disease: An Integrative Stereological and Proteomic Study

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