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

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.

A CRISPR-Cas9-mediated F0 screen to identify pro-regenerative genes in the zebrafish retinal pigment epithelium

“…S1) (Leach et al ., 2021; Lu et al ., 2022) based on predicted functions (e.g. cell-cell contact, lipid metabolism, immune responses) that are critical during tissue regeneration in a variety of organs/systems (Roy and Tedeschi, 2021; George et al ., 2021). To generate knockouts, we modified an existing CRISPR/Cas9-based F0 mutagenesis methodology (Fig.…”

A Brief Analysis of Proteomic Profile Changes during Zebrafish Regeneration

“…Moreover, the regulation of cytoskeleton and metabolic signaling pathways were involved in tissue regeneration for the cell movement, growth, and proliferation [ 33 , 34 ]. Studies showed that the modification of lipid metabolism is needed in liver and axon regeneration [ 35 , 36 ]. Lastly, the assembly and activity of ribosomal proteins are required for protein synthesis and involved in regeneration process [ 37 , 38 ].…”

Protocol for assessing ex vivo lipolysis of murine adipose tissue

“…The same method can be adapted to measure lipolytic potential of brown adipose tissue. Although this technique can reliably detect endogenous lipolytic potential of adipose tissue as a functional readout of metabolic homeostasis in health and disease ( Roy and Tedeschi, 2021 ), it remains an end point assessment. When continuous assessment is necessary, in-situ microdialysis of adipose tissue should be considered as it enables real-time detection of lipolysis in response to an external stimuli like cold exposure ( Arner et al., 1988 ; Weir et al., 2018 ).…”