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Lipids and Brain Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 10884

Special Issue Editor


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Guest Editor
INSERM UMR_S Acute and Chronic Cardiovascular Failure, DCAC, Faculty of Medicine, University of Lorraine, 54505 Vandoeuvre-lès-Nancy, France
Interests: lipid homeostasis; lipoprotein receptors; dyslipidemias; obesity; brain aging; apolipoprotein E; Alzheimer’s disease; inflammation; atherosclerosis
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Special Issue Information

Dear Colleagues,

With the increasing longevity of the general population and, consequently, increased incidence of neurodegenerative diseases including Alzheimer’s disease, the pathophysiology of brain aging has become a subject of interest in research.  

The aim of this Special Issue is to explore lipid-related molecular mechanisms involved in brain aging in health and disease. Indeed, lipids play many roles in the central nervous system, as membrane structural components, in cell signaling and gene expression regulation. Glia were originally considered to be a support system providing lipids and other nutrients to neurons. Now, recent data point to the importance of glia–neuron communication for the functional integrity of the tripartite synapse composed of pre- and postsynaptic membranes and glia. Lipid homeostasis, ensuring a balance between glia-neuron lipid influx and efflux, is a critical determinant of neuron function and synaptic plasticity. The tight regulation of lipid homeostasis involves a system of enzymes, transporters, receptors, and transcription factors involved in lipid metabolism and trafficking between glia and neurons.

The goal of this issue to explore this topic providing a better understanding of the role of lipids and lipid homeostasis in the physiopathology of brain aging, and to identify therapeutics that may be either lipid-based or targeting key lipid-related pathways for the prevention or treatment of brain aging, a risk factor for neurodegenerative diseases.

Original articles or focused reviews addressing these topics will be considered for publication.

Dr. Frances Yen
Guest Editor

Manuscript Submission Information

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Keywords

  • Lipids
  • Lipid homeostasis
  • Brain aging
  • Prevention
  • Therapy
  • Neurodegeneration
  • Alzheimer’s disease

Published Papers (3 papers)

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Research

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16 pages, 2314 KiB  
Article
Lipolysis-Stimulated Lipoprotein Receptor Acts as Sensor to Regulate ApoE Release in Astrocytes
by Ameziane Herzine, Ghita Sekkat, Sandra Kaminski, Gaetano Calcagno, Sandrine Boschi-Muller, Hela Safi, Catherine Corbier, Sophie Siest, Thomas Claudepierre and Frances T. Yen
Int. J. Mol. Sci. 2022, 23(15), 8630; https://doi.org/10.3390/ijms23158630 - 3 Aug 2022
Cited by 2 | Viewed by 2256
Abstract
Astroglia play an important role, providing de novo synthesized cholesterol to neurons in the form of ApoE-lipidated particles; disruption of this process can increase the risk of Alzheimer’s disease. We recently reported that glia-specific suppression of the lipolysis-stimulated lipoprotein receptor (LSR) gene leads [...] Read more.
Astroglia play an important role, providing de novo synthesized cholesterol to neurons in the form of ApoE-lipidated particles; disruption of this process can increase the risk of Alzheimer’s disease. We recently reported that glia-specific suppression of the lipolysis-stimulated lipoprotein receptor (LSR) gene leads to Alzheimer’s disease-like memory deficits. Since LSR is an Apo-E lipoprotein receptor, our objective of this study was to determine the effect of LSR expression modulation on cholesterol and ApoE output in mouse astrocytes expressing human ApoE3. qPCR analysis showed that siRNA-mediated lsr knockdown significantly increased expression of the genes involved in cholesterol synthesis, secretion, and metabolism. Analysis of media and lipoprotein fractions showed increased cholesterol and lipidated ApoE output in HDL-like particles. Further, lsr expression could be upregulated when astrocytes were incubated 5 days in media containing high levels (two-fold) of lipoprotein, or after 8 h treatment with 1 µM LXR agonist T0901317 in lipoprotein-deficient media. In both conditions of increased lsr expression, the ApoE output was repressed or unchanged despite increased abca1 mRNA levels and cholesterol production. We conclude that LSR acts as a sensor of lipoprotein content in the medium and repressor of ApoE release, while ABCA1 drives cholesterol efflux, thereby potentially affecting cholesterol load, ApoE lipidation, and limiting cholesterol trafficking towards the neuron. Full article
(This article belongs to the Special Issue Lipids and Brain Aging)
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18 pages, 1559 KiB  
Article
Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age
by Mariona Jové, Rosanna Cabré, Natàlia Mota-Martorell, Meritxell Martin-Garí, Èlia Obis, Paula Ramos, Iván Canales, José Daniel Galo-Licona, Joaquim Sol, Lara Nogueras, Pascual Torres, Manuel Portero-Otín, Victòria Ayala, Isidro Ferrer and Reinald Pamplona
Int. J. Mol. Sci. 2021, 22(22), 12517; https://doi.org/10.3390/ijms222212517 - 20 Nov 2021
Cited by 9 | Viewed by 2061
Abstract
Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of [...] Read more.
Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)—as an anti-aging intervention—for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age. Full article
(This article belongs to the Special Issue Lipids and Brain Aging)
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Review

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24 pages, 1395 KiB  
Review
Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging
by Ignasi Mora, Lluís Arola, Antoni Caimari, Xavier Escoté and Francesc Puiggròs
Int. J. Mol. Sci. 2022, 23(7), 3472; https://doi.org/10.3390/ijms23073472 - 23 Mar 2022
Cited by 13 | Viewed by 5827
Abstract
Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, [...] Read more.
Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of “omic” technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging. Full article
(This article belongs to the Special Issue Lipids and Brain Aging)
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