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Cited by 68

The DOI matches its Crossref record; 252 of the 252 references it cites were found in a registry or an index.

The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Roy, Debasish, Tedeschi, Andrea·2021·Cells
DOI 10.3390/cells10051078PMC PMC8147289
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Abstract

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

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Crossref · 10.3390/cells10051078

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Figures

Figure 1 Lipids and plasma membrane. (A) Schematic representation of the three major kinds of membrane lipids. (B) Illustration of the typical lipid bilayer of the plasma membrane.
Figure 1 Lipids and plasma membrane. (A) Schematic representation of the three major kinds of membrane lipids. (B) Illustration of the typical lipid bilayer of the plasma membrane.CC BY · PubMed Central
Figure 2 Membrane expansion during nervous system development and repair.
Figure 2 Membrane expansion during nervous system development and repair.CC BY · PubMed Central
Figure 3 The exocyst protein complex.
Figure 3 The exocyst protein complex.CC BY · PubMed Central
Figure 4 Adipose tissue depots, energy balance and leptin sensing. (A) Representation of adipose depots located under the skin and within the abdomen in adult mice. Whereas WAT can be subdivided into subcutaneous, bone marrow and visceral depots, BAT mainly localizes in the interscapular region. (B) Under normal physiological conditions, sympathetic innervation regulates WAT lipolysis and BAT thermogenesis. The contribution of sensory innervation is far less understood. Leptin action on the neurons located in the hypothalamus is critical for homeostatic regulation of energy balance. After SCI, interruption of adipose tissue innervation causes a breakdown in energy homeostasis leading to adipose tissue accumulation and ectopic lipid spillover to vital organs. If protracted, such detrimental conditions contribute to the development of insulin resistance, increased fatty acids, cardiovascular complications and metabolic syndrome.
Figure 4 Adipose tissue depots, energy balance and leptin sensing. (A) Representation of adipose depots located under the skin and within the abdomen in adult mice. Whereas WAT can be subdivided into subcutaneous, bone marrow and visceral depots, BAT mainly localizes in the interscapular region. (B) Under normal physiological conditions, sympathetic innervation regulates WAT lipolysis and BAT thermogenesis. The contribution of sensory innervation is far less understood. Leptin action on the neurons located in the hypothalamus is critical for homeostatic regulation of energy balance. After SCI, interruption of adipose tissue innervation causes a breakdown in energy homeostasis leading to adipose tissue accumulation and ectopic lipid spillover to vital organs. If protracted, such detrimental conditions contribute to the development of insulin resistance, increased fatty acids, cardiovascular complications and metabolic syndrome.CC BY · PubMed Central

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Metadata

Authors
Roy, D., & Tedeschi, A.
Affiliations
Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-05-01
Volume
10
Issue
5
Pages
1078
ISSN
2073-4409
DOI
10.3390/cells10051078
PMC
PMC8147289
Cited by
68
References
252
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS110681, R21NS109787)
  • Chronic Brain Injury Discovery Theme (202001)

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