Agmatine as a potential therapeutic intervention in bipolar depression: the preclinical landscape

Watts, Devon; Pfaffenseller, Bianca; Wollenhaupt-Aguiar, Bianca; Géa, Luíza Paul; Cardoso, Taiane de Azevedo; Kapczinski, Flávio

doi:10.1080/14728222.2019.1581764

Cited by 11 publications

(7 citation statements)

References 140 publications

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“…The literature regarding agmatine has drastically increased over the last decade with a wide range of neurological focuses such as ischemic stroke, epilepsy, and psychological disorders such as stress, depression, and addiction [ 2 , 9 , 17 - 19 ]. Recent studies have shown that agmatine protects neurons against glutamate toxicity by inhibiting the production of NO in microglia; this mechanism is controlled by NMDA receptors [ 20 - 24 ].…”

Section: Agmatine: Overview and Biological Significance In The Central Nervous Systemmentioning

confidence: 99%

“…As previously mentioned, agmatine can be found throughout the mammalian body and plays a role in maintaining homeostasis of the brain, heart and surrounding vascular structure by modulating calcium levels [ 5 , 10 , 11 , 13 ]. There is a wide range of neurological focuses and applications of agmatine such as Alzheimer’s, stroke, epilepsy and psychological disorders such as stress, depression and addiction ( Table 1 ) [ 2 , 17 - 19 , 31 ]. Recent studies have shown that agmatine protects neurons against glutamate toxicity by inhibiting the production of NO in microglia.…”

Section: Therapeutic Application Of Agmatine On Neuronal Progenitor Cell Therapy In the Central Nervous System Diseasementioning

confidence: 99%

“…The simulation and increased proliferation of neural progenitor cells in the hippocampus is known to decrease or reduce depressive-like symptoms [ 23 ]. With multiple studies displaying results that agmatine increases the proliferation of hippocampal progenitor cells, this mechanism provides an anti-depressive like effect [ 9 , 18 , 34 ]. Targeting hippocampal progenitor cells in chronically stress-induced mice, agmatine increases neurogenesis, leading to a decrease in depressive behaviors [ 9 ].…”

Section: Therapeutic Application Of Agmatine On Neuronal Progenitor Cell Therapy In the Central Nervous System Diseasementioning

confidence: 99%

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Role of agmatine in the application of neural progenitor cell in central nervous system diseases: therapeutic potentials and effects

et al. 2021

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Agmatine, the primary decarboxylation product of L-arginine, generated from arginine decarboxylase. Since the discovery of agmatine in the mammalian brain in the 1990s, an increasing number of agmatine-mediated effects have been discovered, demonstrating the benefits of agmatine on ischemic strokes, traumatic brain injury and numerous psychological disorders such as depression, anxiety, and stress. Agmatine also has cellular protective effects and contributes to cell proliferation and differentiation in the central nervous system (CNS). Neural progenitor cells are an important component in the recovery and repair of many neurological disorders due to their ability to differentiate into functional adult neurons. Recent data has revealed that agmatine can regulate and increase proliferation and the fate of progenitor cells in the adult hippocampus. This review aims to summarise and discuss the role of agmatine in the CNS; specifically, the effects and relationship between agmatine and neural progenitor cells and how these ideas can be applied to potential therapeutic application.

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Section: Agmatine: Overview and Biological Significance In The Central Nervous Systemmentioning

confidence: 99%

Section: Therapeutic Application Of Agmatine On Neuronal Progenitor Cell Therapy In the Central Nervous System Diseasementioning

confidence: 99%

Section: Therapeutic Application Of Agmatine On Neuronal Progenitor Cell Therapy In the Central Nervous System Diseasementioning

confidence: 99%

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Role of agmatine in the application of neural progenitor cell in central nervous system diseases: therapeutic potentials and effects

et al. 2021

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“…2 It has been suggested that states of chronic stress lead to impairments in both blood-brain barrier and epithelial gut barrier permeability, but not necessarily by the same mechanisms. [7][8][9] The information on changes in tight junction proteins in response to stress stimuli is limited. Exposure of mice to chronic unpredictable restraint stress resulted in intestinal hyperpermeability associated with a decrease in zonula occludens protein-1 (ZO-1) and occludin expression in the colon.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to the endothelial cells of the brain capillaries, the epithelial cells form barriers, such as the gut barrier, which are much more leaky and have much greater variability of claudin expression 2 . It has been suggested that states of chronic stress lead to impairments in both blood‐brain barrier and epithelial gut barrier permeability, but not necessarily by the same mechanisms 7–9 …”

Section: Introductionmentioning

confidence: 99%

Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Karailiev

Hlavacova

Chmelova

et al. 2021

Neurogastroenterology Motil

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Background: Simultaneous evaluation of barrier protein expression in the gut and the brain and their modulation under stress conditions have not been studied before now. As the permeability and function of the gut and blood-brain barrier are different and both express the MRs, we hypothesized that stress of post-weaning social isolation induces changes in tight junction protein expression in the gut which are (1) independent of changes in the brain and (2) are mediated via the mineralocorticoid receptor (MR).Methods: First, using UPLC-MS/MS we have successfully validated and selected a dose (1.2 mg/rat/day) of the MR antagonist spironolactone to treat female rats exposed to stress of chronic isolation or control conditions from postnatal day 21 for 9 weeks. Key Results: Isolation stress caused an enhancement of gene expression of occludin and ZO-1 and a decrease in claudin-5 and MR expression in both the small intestine and prefrontal cortex. Isolation stress failed to decrease claudin-5 (small intestine) and MR (prefrontal cortex) gene expression in spironolactone-treated rats. MR blockade resulted in a decrease in claudin-15 expression in the small intestine. Anxiogenic effect of chronic stress, measured in elevated plus-maze test, was partly prevented by spironolactone treatment. Conclusions & Inferences:Claudins, the main regulators of intestinal barrier permeability responded to chronic stress of social isolation and/or simultaneous blockade of MR in female rats by alterations independent of changes in the brain cortex. The results suggest a physiological role of MR in the control of claudin expression in the small intestine, but not in the brain cortex.

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Enhancing anti-tumor therapy with agmatine-cholesterol conjugate liposomes: in vitro and in vivo evidence

Wang,

Chang

et al. 2023

Drug Deliv. and Transl. Res.

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In this study, we synthesized a novel compound, agmatine-cholesterol conjugate (AG-Chol), to enhance the anti-tumor activity of liposomes. We used AG-Chol to replace cholesterol in preparing doxorubicin hydrochloride (DOX) liposomes by an active loading method. We assessed the physical and chemical properties of the resulting liposomes (AG-Liposomes) and evaluated their e cacy in vitro and in vivo. The results showed that AG-Liposomes were stable with high encapsulation e ciency. Compared with the control liposomes, AG-Liposomes exhibited a slower release rate in the release medium at pH 6.8. The in vitro cell experiments demonstrated that AG-Liposomes had higher tumor cell uptake, migration inhibition rate, apoptosis rate, anti-clonogenic ability, and lysosome escape ability than the control liposomes. In vivo distribution results demonstrate that liposomes prepared with AG-Chol instead of cholesterol can signi cantly enhance their tumor targeting abilities and reduce their distribution to non-targeted sites. In vivo tumor suppression experiments showed that AG-Liposomes had a higher tumor suppression rate than the control liposomes without apparent toxicity, as evidenced by histological staining. Therefore, substituting cholesterol with AG-Chol in the preparation of liposomes can result in enhanced lysosome escape, improved tumor targeting, and increased e cacy of anti-tumor drugs.

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Agmatine as a potential therapeutic intervention in bipolar depression: the preclinical landscape

Cited by 11 publications

References 140 publications

Role of agmatine in the application of neural progenitor cell in central nervous system diseases: therapeutic potentials and effects

Role of agmatine in the application of neural progenitor cell in central nervous system diseases: therapeutic potentials and effects

Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Enhancing anti-tumor therapy with agmatine-cholesterol conjugate liposomes: in vitro and in vivo evidence

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