Chronic infusion of Wnt7a, Wnt5a and Dkk-1 in the adult hippocampus induces structural synaptic changes and modifies anxiety and memory performance

Ortiz‐Matamoros, Abril; Arias, Clorinda

doi:10.1016/j.brainresbull.2018.03.008

Cited by 16 publications

(5 citation statements)

References 49 publications

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“…Therefore, it is feasible to speculate that chronically infused Wnt5a might increase the basal hippocampal excitability, and also participates in the development of the abnormal pattern of neurite growth we found. Although we did not observe behavioral changes suggesting epileptiform activity, rats infused with the agonist Wnt5a were more active in the open field as we previously reported (Ortiz‐Matamoros and Arias, ).…”

Section: Discussionsupporting

confidence: 58%

“…In a model previously reported, we showed the efficiency of the chronic infusion of Wnt ligands on hippocampal structure and in the activation of canonical Wnt signaling (Ortiz‐Matamoros and Arias, ). In the present study, we first studied the effects of the agonists and the canonical antagonist of the Wnt pathway on neuronal viability in the DG, by cresyl violet and NeuN stained after 10 days of the infusion of Wnt‐related molecules.…”

Section: Resultsmentioning

confidence: 76%

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Differential Changes in the Number and Morphology of the New Neurons after Chronic Infusion of Wnt7a, Wnt5a, and Dkk‐1 in the Adult Hippocampus In Vivo

Ortiz‐Matamoros

Arias

2019

The Anatomical Record

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In the adult hippocampus of many mammals, a particular microenvironment in the neurogenic niche regulates the proliferation, self-renewal, and differentiation of neuronal stem cells. In this proliferative niche, a variety of molecules provide a finely regulated molecular signaling that controls stem cell properties. During development, Wnt signaling has been implicated in cell fate determination and proliferation, in the establishment of cell polarity, as well as a cue for axonal growth and dendrite orientation. In the adult brain, this pathway also participates in the stem cell self-renewal and neuronal differentiation. However, the effects of the chronic Wnt signaling modulation in the adult hippocampus, through the infusion of Wnt7a, Wnt5a, and Dkk-1, on the rate of neurogenesis and on the induction of neurite arborization have not been studied. In this study, we show that Wnt7a and Wn5a further increased the rate of newly generated neurons. However, Wnt5a exerted additional effects by promoting neurite growth and neurite misorientation in the dentate gyrus of adult rats. The chronic exposure to Dkk-1 also generated aberrant location of growing neurites. These results suggest that the interplay of canonical and non-canonical Wnt ligands participates in neuronal stem cell proliferation and in the establishment of proper neurite maturation.

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Section: Discussionsupporting

confidence: 58%

Section: Resultsmentioning

confidence: 76%

Differential Changes in the Number and Morphology of the New Neurons after Chronic Infusion of Wnt7a, Wnt5a, and Dkk‐1 in the Adult Hippocampus In Vivo

Ortiz‐Matamoros

Arias

2019

The Anatomical Record

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“…Furthermore, the sEHI down-regulated DE miRNAs, miR-5125, and miR-692, and their targets, DKK1 and PKC, respectively. Inhibition of DKK1 has been shown to improve cognitive impairment [90] and protect against neurotoxicity [91]. PKC inhibition also protects against vascular injury of the blood-brain barrier [74].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

et al. 2021

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Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH.

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“…Some scholars suggest that the endogenous Wnt ligands, which are inhibited by DKK1, are vital to maintaining the neuronal synapses (Purro et al, 2014). Also, the potential therapeutic effects of the DKK1 inhibitor may be associated with synaptic preservation and hippocampal circuit reconstruction (Marzo et al, 2016;Ortiz-Matamoros and Arias, 2018). Animal tests show that inhibiting DKK1 improves subjects' spatial memory tasks (Marzo et al, 2016;Ortiz-Matamoros and Arias, 2018) and their electrophysiological findings (Marzo et al, 2016).…”

Section: Dkk1mentioning

confidence: 99%

Regulatory Roles of Bone in Neurodegenerative Diseases

Ling

Lü

et al. 2020

Front. Aging Neurosci.

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Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

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Chronic infusion of Wnt7a, Wnt5a and Dkk-1 in the adult hippocampus induces structural synaptic changes and modifies anxiety and memory performance

Cited by 16 publications

References 49 publications

Differential Changes in the Number and Morphology of the New Neurons after Chronic Infusion of Wnt7a, Wnt5a, and Dkk‐1 in the Adult Hippocampus In Vivo

Differential Changes in the Number and Morphology of the New Neurons after Chronic Infusion of Wnt7a, Wnt5a, and Dkk‐1 in the Adult Hippocampus In Vivo

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

Regulatory Roles of Bone in Neurodegenerative Diseases

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