OCN can pass through the blood–brain barrier (BBB) and modulating the monoamine neurotransmitters and favoring learning and memory of mice. Besides its regulations of glucose metabolism, lipid metabolism, muscle power, and male fertility, an intriguing role of OCN in CNS is being revealed. Osteocalcin (OCN), a polypeptide secreted exclusively by osteoblasts, exerts multiple endocrine functions through its metabolically active undercarboxylated form (ucOCN). Thus, safe and effective molecules are needed to be discovered. However, there are currently few these kinds of drugs in the market. Thus, targeting glycolysis in neuroglia, especially in astrocytes, may be a promising therapy for AD treatment. On the other hand, increasing aerobic glycolysis ameliorates the Aβ-induced activation of astrocytes and improves the spatial cognition in AD mice. In cultures of human fetal astrocytes, inhibition of main enzymatic regulator of glycolysis results in increased accumulation of Aβ within and around astrocytes and greater vulnerability of these cells to Aβ toxicity. Alteration of brain aerobic glycolysis is often observed early in the course of AD. Astrocyte-derived lactate is taken by neurons and converted to pyruvate and further undergoes oxidative phosphorylation (OXPHOS) to fuel neuronal activity. Specifically, astrocytes absorb glucose from blood and produce lactate via aerobic glycolysis. Neuroglial cells, which mainly consist of astrocytes and microglia in central nervous system (CNS), function as the supporter for neurons by maintaining the microenvironment in CNS. However, Aβ-targeted therapeutics for AD have not yet proven to benefit significantly in clinical practice, which drives researches to explore new mechanisms and treatments. Accumulation of Aβ in cognition-related brain regions is the primary factor driving AD pathogenesis. Our study revealed OCN as a novel therapeutic factor for AD potentially through reducing Aβ burden and upregulation of glycolysis in neuroglia.Īlzheimer’s disease (AD) is the most common neurodegenerative disease which causes a progressive decline of cognition, and for which there is no cure. Such an effect was abolished when the receptor of OCN – Gpr158 was knockdown in astrocytes. Furthermore, OCN enhanced glycolysis in astrocytes and microglia, as evidenced by elevated glucose consumption, lactate production, and increased extracellular acidification rate. The proliferation of astrocytes in the hippocampus in AD mice was also inhibited by OCN as demonstrated by immunofluorescence. Besides, OCN improved the neural network function of the brain, mainly in the enhanced power of high gamma band in the medial prefrontal cortex of AD mice. Aβ burden in the hippocampus and cortex of AD mice was ameliorated by OCN. In this study, daily intraperitoneal injection of OCN for 4 weeks ameliorated the anxiety-like behaviors and cognitive dysfunctions in the APP/PS1 transgenic AD mice model, as shown in the increased entries into the central area in open field test, the increased time and entries into open arms in elevated plus maze test, the increased time spent in the light chamber in light-dark transition test, as well as the reduced escape latency and the increased preference for target quadrant in Morris water maze test. Osteocalcin (OCN), an osteoblast-derived protein, has been shown to modulate brain functions but whether it has any effect on AD is undetermined. ISBN 9780231551304.Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the accumulation of amyloid β peptides (Aβ) and impaired glucose metabolism in the brain. The chile pepper in China : a cultural biography. Journal of Fujian Agriculture and Forestry University (Natural Science Edition). ^ "Genetic diversity and relationship analysis of pepper germplasm resources based on phenotype traits and SRAP molecular marker".conoides (Mill.) Irish, Synonym of Capsicum annuum L. ^ " Capsicum annuum L." Plants of the World Online.^ a b " Capsicum annuum (Conioides group) (Biberi Pepper, Cone Pepper, Conic Pepper, Facing Heaven Pepper) | North Carolina Extension Gardener Plant Toolbox".
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