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Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

ABSTRACT: Cognitive deficits are widespread in psychiatric disorders, including major depression and schizophrenia. These deficits are known to contribute significantly to the accompanying functional impairment. Progress in the development of targeted treatments of cognitive deficits has been limited and there exists a major unmet need to develop more efficacious treatments. Erythropoietin (Epo) has shown promising procognitive effects in psychiatric disorders, providing support for a neurotrophic drug development approach. Several preclinical studies with non-erythropoietic derivatives have demonstrated that the modulation of behavior is independent of erythropoiesis. In this review, we examine the molecular, cellular and cognitive actions of Epo and non-erythropoietic molecular derivatives by focusing on their neurotrophic, synaptic, myelin plasticity, anti-inflammatory and neurogenic mechanisms in the brain. We also discuss the role of receptor signaling in Epo and non-erythropoietic EPO-mimetic molecules in their procognitive effects.

SUBMITTER: Newton SS

PROVIDER: S-EPMC8450392 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

Newton Samuel S SS Sathyanesan Monica M

Frontiers in pharmacology 20210906

Cognitive deficits are widespread in psychiatric disorders, including major depression and schizophrenia. These deficits are known to contribute significantly to the accompanying functional impairment. Progress in the development of targeted treatments of cognitive deficits has been limited and there exists a major unmet need to develop more efficacious treatments. Erythropoietin (Epo) has shown promising procognitive effects in psychiatric disorders, providing support for a neurotrophic drug de ...[more]

PMID: 34552490

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Project description:Garlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects.

Dataset Information

Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

Publications

Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

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