Mini review: Lipids in Peripheral Nerve Disorders

Hornemann, T.

doi:10.1016/j.neulet.2020.135455

Cited by 19 publications

(13 citation statements)

References 92 publications

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“…Of all human tissues, the brain has the second-highest lipid content after adipose tissues, accounting for 50% of its dry weight ( 37 ). Brain lipids mainly consist of cholesterol, phospholipids, such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and sphingolipids ( Fig.…”

Section: Brain Lipidsmentioning

confidence: 99%

Brain lipidomics: From functional landscape to clinical significance

et al. 2022

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Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities.

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Section: Brain Lipidsmentioning

confidence: 99%

Brain lipidomics: From functional landscape to clinical significance

et al. 2022

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“…Lipids contribute to the structural integrity and physical characteristics of cell and organelle membranes, act as bioactive signaling molecules, function in energy storage, and maintain homeostasis. 37,38 Brain lipids mainly consist of cholesterol, phospholipids such as phosphatidylcholine and phosphatidylethanolamine, and sphingolipids. Two major changes in phospholipid metabolism in females because of EC exposure include a decrease in cytidine 5'-diphosphocholine and an increase in glycerophosphorylcholine and trimethylamine N-oxide.…”

Section: Discussionmentioning

confidence: 99%

Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats

Pradhyumnan,

Patel,

Furones-Alonso

et al. 2024

Stroke

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BACKGROUND: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes. METHODS: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis. RESULTS: In females, EC significantly increased ( P <0.05) infarct volumes by 94% as compared with air-exposed rats, 165±50 mm 3 in EC-exposed rats, and 85±29 mm 3 in air-exposed rats, respectively, while in males such a difference was not apparent. Morris water maze data showed significant deficits in spatial learning and working memory in the EC sham or transient middle cerebral artery occlusion groups compared with the respective air groups in rats of both sexes ( P <0.05). Thirty-two metabolites of carbohydrate, glycolysis, tricarboxylic acid cycle, and lipid metabolism were significantly altered ( P ≤0.05) due to EC, 23 of which were specific for females. Steady-state protein levels of hexokinase significantly decreased ( P <0.05) in EC-exposed females; however, these changes were not seen in males. CONCLUSIONS: Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats.

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“…These results parallel previous studies in murine models and humans with metabolic syndrome, prediabetes, and T2D ( O'Brien et al, 2020 ; Rumora et al, 2021 ), suggesting that changes in nerve phospholipids contribute to large fiber PN pathogenesis in these disease states. Phospholipids make up approximately 57% of lipids in the cell bodies and axons of peripheral neurons and 40% of lipids in the myelin sheath ( Calderon et al, 1995 ; Poitelon et al, 2020 ; Hornemann, 2021 ). Alterations in phospholipid levels can trigger aberrant changes in cellular signaling ( Nishizuka, 1992 ), cell membrane structure ( Kuge et al, 2014 ), and membrane dynamics in neurons ( Tracey et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by reports showing decreased plasma SM levels in patients with T2D ( Rumora et al, 2021 ) and obesity ( Guo et al, 2021 ). SM is an important nerve lipid of the myelin sheath, which protects and supports sensory nerve fibers ( Poitelon et al, 2020 ; Hornemann, 2021 ). Although the role of LPE in the peripheral nervous system is less studied, changes in LPE levels are reported in other neurological disorders, including Alzheimer’s disease ( Liu et al, 2021 ; Llano et al, 2021 ), emphasizing the importance of this lipid for proper nervous system function.…”

Section: Discussionmentioning

confidence: 99%

A High-Fat Diet Disrupts Nerve Lipids and Mitochondrial Function in Murine Models of Neuropathy

et al. 2022

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As the prevalence of prediabetes and type 2 diabetes (T2D) continues to increase worldwide, accompanying complications are also on the rise. The most prevalent complication, peripheral neuropathy (PN), is a complex process which remains incompletely understood. Dyslipidemia is an emerging risk factor for PN in both prediabetes and T2D, suggesting that excess lipids damage peripheral nerves; however, the precise lipid changes that contribute to PN are unknown. To identify specific lipid changes associated with PN, we conducted an untargeted lipidomics analysis comparing the effect of high-fat diet (HFD) feeding on lipids in the plasma, liver, and peripheral nerve from three strains of mice (BL6, BTBR, and BKS). HFD feeding triggered distinct strain- and tissue-specific lipid changes, which correlated with PN in BL6 mice versus less robust murine models of metabolic dysfunction and PN (BTBR and BKS mice). The BL6 mice showed significant changes in neutral lipids, phospholipids, lysophospholipids, and plasmalogens within the nerve. Sphingomyelin (SM) and lysophosphatidylethanolamine (LPE) were two lipid species that were unique to HFD BL6 sciatic nerve compared to other strains (BTBR and BKS). Plasma and liver lipids were significantly altered in all murine strains fed a HFD independent of PN status, suggesting that nerve-specific lipid changes contribute to PN pathogenesis. Many of the identified lipids affect mitochondrial function and mitochondrial bioenergetics, which were significantly impaired in ex vivo sural nerve and dorsal root ganglion sensory neurons. Collectively, our data show that consuming a HFD dysregulates the nerve lipidome and mitochondrial function, which may contribute to PN in prediabetes.

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Mini review: Lipids in Peripheral Nerve Disorders

Cited by 19 publications

References 92 publications

Brain lipidomics: From functional landscape to clinical significance

Brain lipidomics: From functional landscape to clinical significance

Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats

A High-Fat Diet Disrupts Nerve Lipids and Mitochondrial Function in Murine Models of Neuropathy

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