Retrograde axonal transport of LIF is increased by peripheral nerve injury: Correlation with increased LIF expression in distal nerve

Curtis, Rory; Scherer, Steven S.; Somogyi, Robert; Adryan, Krystyna M.; Ip, Nancy Y.; Zhu, Yuan; Lindsay, Ronald M.; DiStefano, Peter S.

doi:10.1016/0896-6273(94)90163-5

Cited by 265 publications

(182 citation statements)

References 62 publications

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“…LIF expression, in contrast, is also detected at earlier stages (Banner and Patterson, 1994). However, only very low levels of LIF mRNA are expressed in intact postnatal nerves, but a rapid and dramatic increase occurs when nerves are lesioned (Banner and Patterson, 1994;Curtis et al, 1994;Sun et al, 1996). LIF acts as an autocrine survival factor for Schwann cells (Dowsing et al, 1999) and may play a role as a regulator of macrophage attraction to the lesioned nerve (Tofaris et al, 2002).…”

Section: Discussionmentioning

confidence: 95%

“…First, CT-1 is expressed in skeletal muscle (Pennica et al, 1996), whereas Schwann cells are the major source of CNTF (Stockli et al, 1991;Friedman et al, 1992;Rende et al, 1992) and LIF (Banner and Patterson, 1994;Curtis et al, 1994). Second, the developmental time course of CNTF mRNA expression differs significantly from that of LIF and CT-1.…”

Section: Discussionmentioning

confidence: 99%

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Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Holtmann¹,

Wiese²,

Samsam³

et al. 2005

J. Neurosci.

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Members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor (LIF) gene family play an essential role for survival of developing and postnatal motoneurons. When subunits of the shared receptor complex are inactivated by homologous recombination, the mice die at approximately birth and exhibit reduced numbers of motoneurons in the spinal cord and brainstem nuclei. However, mice in which cntf, lif, or cardiotrophin-1 (ct-1) are inactivated can survive and show less motoneuron cell loss. This suggests cooperative and redundant roles of these ligands. However, their cooperative functions are not well understood. We generated cntf/lif/ct-1 triple-knockout and combinations of double-knock-out mice to study the individual and combined roles of CNTF, LIF and CT-1 on postnatal motoneuron survival and function. Triple-knock-out mice exhibit increased motoneuron cell loss in the lumbar spinal cord that correlates with muscle weakness during early postnatal development. LIF deficiency leads to pronounced loss of distal axons and motor endplate alterations, whereas CNTF-and/or CT-1-deficient mice do not show significant changes in morphology of these structures. In cntf/lif/ct-1 triple-knock-out mice, various degrees of muscle fiber type grouping are found, indicating that denervation and reinnervation had occurred. We conclude from these findings that CNTF, LIF, and CT-1 have distinct functions for motoneuron survival and function and that LIF plays a more important role for postnatal maintenance of distal axons and motor endplates than CNTF or CT-1.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Holtmann¹,

Wiese²,

Samsam³

et al. 2005

J. Neurosci.

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“…The mRNA for LIF is upregulated in the neurons and glia of human patients with subacute sclerosing panencephalitis, a long-term inflammatory measles virus infection [105]. A dramatic rise in LIF mRNA is also observed following sciatic or olfactory nerve transection, cortical stab wound, excitatory amino acid-induced injury to the spinal cord, and seizure [106][107][108][109][110][111][112]. In LIF KO mice, infiltration by neutrophils, macrophages, and mast cells is delayed compared with wildtype in both CNS and PNS lesions [113,114].…”

Section: Lif In Neural Inflammationmentioning

confidence: 90%

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

1999

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Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.

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“…Peripheral nerve damage up-regulates the expression of the cytokines LIF (44) and by Schwann cells within the nerve, and in the case of IL-6, in the DRG neurons themselves (37). These changes markedly increase the levels of galanin in the DRG (37,38).…”

Section: Discussionmentioning

confidence: 99%

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

Holmes

Mahoney²,

King³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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193

171

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The neuropeptide galanin is expressed developmentally in the dorsal root ganglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve section in the adult. Here we report that adult mice carrying a loss-of-function mutation in the galanin gene have a 13% reduction in the number of cells in the DRG associated with a 24% decrease in the percentage of neurons that express substance P. These deficits are associated with a 2.8-and 2.6-fold increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4, respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrate similar deficits in neurite number and length. These results identify a critical role for galanin in the development and regeneration of sensory neurons. D amage to a peripheral nerve causes changes within the cell body that promote neuronal survival, axonal regeneration, and functional recovery. Under favorable conditions, for instance after a crush injury, most nerve fibers successfully regenerate. However, in many clinically relevant circumstances, traumatic or disease-induced nerve injury has a poor outcome with only limited return of function and often with considerable delay. The molecular and cellular interactions that control the degree and rate of peripheral nerve regeneration are poorly understood and remain important clinical and scientific issues.In an attempt to define the mechanisms that regulate neuronal survival and regeneration, we and others have used the approach of studying factors whose expression patterns are known to change in response to injury. One of the most potent changes in the dorsal root ganglion (DRG) after peripheral nerve injury is the 120-fold increase in the levels of the 29-aa neuropeptide galanin (1). Studies have demonstrated that galanin is expressed at high levels in most cells of the developing DRG from day 16 of gestation until shortly after birth (2). In the adult, galanin is expressed at low levels in only 2-3% of DRG cells, which are predominantly small fiber neurons (1). After axotomy, mRNA and peptide are abundantly expressed in 40-50% of all DRG neurons (3) and remain elevated while the nerve is regenerating (1). Similarly, axotomy also up-regulates galanin expression in motor (4) and sympathetic (5) neurons. The rise in expression in the dorsal horn after axotomy is modest compared with the marked elevation in the DRG (6), reflecting an increase in anterograde transport of galanin from the cell body to the site of injury (7), analogous to that described in axotomized sympathetic neurons (8). Despite these findings, there is no direct evidence that galanin plays a role in axonal regeneration after injury.We previously have generated mice carrying a loss-of-function mutation in the galanin gene (9) and most recently have demonstrated that the chronic absence of galanin throughout prenatal and postnatal development causes an atte...

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Retrograde axonal transport of LIF is increased by peripheral nerve injury: Correlation with increased LIF expression in distal nerve

Cited by 265 publications

References 62 publications

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

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