The role of sphingolipids in neuronal plasticity of the brain

Sonnino, Sandro; Prinetti, Alessandro

doi:10.1111/jnc.13589

Cited by 36 publications

(21 citation statements)

References 14 publications

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“…Accumulation of sphingolipids has been noted in various cancers such as tumors of the head and neck, lung cancer, sarcomas, breast cancer and endometrial cancer. There are studies showing that certain tumors, including colon cancer and brain cancer, are characterized by decreased concentration of ceramides compared to healthy tissues [18,19]. Such data clearly indicate that sphingolipid metabolism is closely associated with cell transformation depending on histological type of the tissue.…”

Section: Discussionmentioning

confidence: 97%

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Knapp

Bodnar

Błachnio-Zabielska

et al. 2017

Gynecologic Oncology

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Section: Discussionmentioning

confidence: 97%

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Knapp

Bodnar

Błachnio-Zabielska

et al. 2017

Gynecologic Oncology

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“…The influence of ovarian hormones on the dietary effects on cortical ceramides is highly relevant given the important function of these lipids in a wide range of cell processes including growth, differentiation, apoptosis, and oncogenesis (Kashara and Sanai, 2000 ; Simons and Toomre, 2000 ; Anderson and Jacobson, 2002 ; Sengupta et al, 2007 ; Pruett et al, 2008 ). Increase in ceramide concentration in cell membranes affects not only the structural organization and dynamic properties of lipid rafts (Cremesti et al, 2002 ) but also myelin formation and stability (Pan et al, 2005 ; Susuki et al, 2007 ), neural differentiation (Wang and Yu, 2013 ; Wang et al, 2014 ), synapse formation (Hering et al, 2003 ; Mendez-Otero and Santiago, 2003 ), synaptic plasticity and transmission, neurotoxicity, and neurodegeneration (Hering et al, 2003 ; Besshoh et al, 2005 ; Ferrer, 2009 ; Fabelo et al, 2014 ; Attiori Essis et al, 2015 ; Sonnino and Prinetti, 2016 ; Marín et al, 2017 ). In addition to experimental evidence in rodents, a number of postmortem studies support the role of age-dependent or genetic alterations of ceramide and sphingolipid metabolism in several neurological disorders, including Alzheimer's (AD) and Parkinson's diseases (He et al, 2010 ; Fabelo et al, 2011 ; Gegg et al, 2012 ; Bouti et al, 2016 ; Olsen and Færgeman, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

Herrera

Ordóñez-Gutiérrez

Fabriás

et al. 2018

Front. Cell. Neurosci.

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Different dietary ratios of n−6/n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n−6/n−3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n−3 and n−6 LC-PUFAs.

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“…Since the oxidized redox potentials of Cys/CySS in human plasma were positively corelated with interleukin-1␤ levels [111], our results of an oxidative shift with age in neurons (Dong, Digman, Brewer, unpublished data) could promote inflammation. Additionally, sphingolipids mediate synaptic plasticity [112], and disturbances in sphingolipid content correlated with impairment in memory and learning [113]. Studies of 30 human plasma samples from each group of AD, MCI, and normal control subjects revealed remarkable declines in sphingomyelin, especially in females [114].…”

Section: Sphingolipidsmentioning

confidence: 99%

Global Metabolic Shifts in Age and Alzheimer’s Disease Mouse Brains Pivot at NAD+/NADH Redox Sites

Dong

Brewer

2019

JAD

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Age and Alzheimer's disease (AD) share some common features such as cognitive impairments, memory loss, metabolic disturbances, bioenergetic deficits, and inflammation. Yet little is known on how systematic shifts in metabolic networks depend on age and AD. In this work, we investigated the global metabolomic alterations in non-transgenic (NTg) and triple-transgenic (3xTg-AD) mouse brain hippocampus as a function of age by using untargeted Ultrahigh Performance Liquid Chromatography-tandem Mass Spectroscopy (UPLC-MS/MS). We observed common metabolic patterns with aging in both NTg and 3xTg-AD brains involved in energy-generating pathways, fatty acids oxidation, glutamate, and sphingolipid metabolism. We found age-related downregulation of metabolites from reactions in glycolysis that consumed ATP and in the TCA cycle, especially at NAD + /NADH-dependent redox sites, where age-and AD-associated limitations in the free NADH may alter reactions. Conversely, metabolites increased in glycolytic reactions in which ATP is produced. With age, inputs to the TCA cycle were increased including fatty acid ␤-oxidation and glutamine. Overall age-and AD-related changes were > 2-fold when comparing the declines of upstream metabolites of NAD + /NADH-dependent reactions to the increases of downstream metabolites (p = 10 −5 , n = 8 redox reactions). Inflammatory metabolites such as ceramides and sphingosine-1phosphate also increased with age. Age-related decreases in glutamate, GABA, and sphingolipid were seen which worsened with AD genetic load in 3xTg-AD brains, possibly contributing to synaptic, learning-and memory-related deficits. The data support the novel hypothesis that age-and AD-associated metabolic shifts respond to NAD(P) + /NAD(P)H redox-dependent reactions, which may contribute to decreased energetic capacity.

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The role of sphingolipids in neuronal plasticity of the brain

Cited by 36 publications

References 14 publications

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

Global Metabolic Shifts in Age and Alzheimer’s Disease Mouse Brains Pivot at NAD+/NADH Redox Sites

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