Lipoprotein lipase is expressed in rat sciatic nerve and regulated in response to crush injury

Huey, Patricia Uelmen; Waugh, Kathleen; Etienne, J; Eckel, Robert H.

doi:10.1016/s0022-2275(20)30182-6

Cited by 24 publications

(3 citation statements)

References 26 publications

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“…7 and 8). LPL is involved in fatty acid metabolism including scavenging of myelin-derived lipid and Aβ phagocytosis [68][69][70][71][72]. Lpl expression is also significantly diminished in the absence of Trem2 in neurogenerative disease and aged mice [7,9,73].…”

Section: Discussionmentioning

confidence: 99%

Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination

Hwang

Savarin

Kim

et al. 2022

J Neuroinflammation

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Background Triggering receptor expressed on myeloid cells 2 (Trem2) plays a protective role in neurodegenerative diseases. By contrast, Trem2 functions can exacerbate tissue damage during respiratory viral or liver infections. We, therefore, investigated the role of Trem2 in a viral encephalomyelitis model associated with prominent Th1 mediated antiviral immunity leading to demyelination. Methods Wild-type (WT) and Trem2 deficient (Trem2−/−) mice were infected with a sublethal glia tropic murine coronavirus (MHV–JHM) intracranially. Disease progression and survival were monitored daily. Leukocyte accumulation and pathological features including demyelination and axonal damage in spinal cords (SC) were determined by flow cytometry and tissue section immunofluorescence analysis. Expression of select inflammatory cytokines and chemokines was measured by RT-PCR and global myeloid cell gene expression in SC-derived microglia and infiltrated bone-marrow-derived macrophages (BMDM) were determined using the Nanostring nCounter platform. Results BMDM recruited to SCs in response to infection highly upregulated Trem2 mRNA compared to microglia coincident with viral control. Trem2 deficiency did not alter disease onset or severity, but impaired clinical recovery after onset of demyelination. Disease progression in Trem2−/− mice could not be attributed to altered virus control or an elevated proinflammatory response. A prominent difference was increased degenerated myelin not associated with the myeloid cell markers IBA1 and/or CD68. Gene expression profiles of SC-derived microglia and BMDM further revealed that Trem2 deficiency resulted in impaired upregulation of phagocytosis associated genes Lpl and Cd36 in microglia, but a more complex pattern in BMDM. Conclusions Trem2 deficiency during viral-induced demyelination dysregulates expression of other select genes regulating phagocytic pathways and lipid metabolism, with distinct effects on microglia and BMDM. The ultimate failure to remove damaged myelin is reminiscent of toxin or autoimmune cell-induced demyelination models and supports that Trem2 function is regulated by sensing tissue damage including a dysregulated lipid environment in very distinct inflammatory environments.

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Section: Discussionmentioning

confidence: 99%

Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination

Hwang

Savarin

Kim

et al. 2022

J Neuroinflammation

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“…3f). From the gene expression programs of the macrophages in diabetic nerves, we identified differentially expressed genes between recMacs and resMacs and found many injury-responsive genes such as Fn1 and Chil3 4 , as well as genes responsible for lipid uptake such as Lpl [24][25][26][27] and genes previously shown to promote nerve regeneration such as Lgals3 and Thbs1 27-29 (Fig. 3e).…”

Section: Macrophages Recruited Into Diabetic Nerves Resemble Those Re...mentioning

confidence: 98%

Macrophages protect against sensory axon degeneration in diabetic neuropathy

Woolf,

Hakim,

Jain

et al. 2024

Preprint

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Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia3, the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and its metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is detectable. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages4 and express neurodegeneration-associated microglia marker genes5 although there is no axon loss or demyelination yet. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings reveal a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.

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Section: Macrophages Recruited Into Diabetic Nerves Resemble Those Re...mentioning

confidence: 99%

Macrophages protect against sensory axon degeneration in diabetic neuropathy

Hakim,

Jain,

Petrova

et al. 2024

Preprint

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Diabetic peripheral neuropathy (DPN) is the most common peripheral nervous system complication of diabetes, causing sensory loss and debilitating neuropathic pain. Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia, the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and the diabetic metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is observed. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages and express neurodegeneration-associated microglia marker genes although there is no axon loss or demyelination yet. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings identify a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.

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Lipoprotein lipase is expressed in rat sciatic nerve and regulated in response to crush injury

Cited by 24 publications

References 26 publications

Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination

Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination

Macrophages protect against sensory axon degeneration in diabetic neuropathy

Macrophages protect against sensory axon degeneration in diabetic neuropathy

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