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Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1).

ABSTRACT: The survival of central neurons depends on multiple neurotrophic factors produced by different cell types. We demonstrate that media conditioned by muscle and Schwann cell lines show strong synergistic effects on survival of purified embryonic day 14.5 rat motoneurons in culture. Different lines of evidence implicate glial cell line-derived neurotrophic factor (GDNF) and cardiotrophin-1 (CT-1) in this synergy. Their expression in the environment of the motoneuron is compartmentalized: gdnf transcripts are expressed principally in Schwann cell lines, whereas ct-1 mRNA is present in myotubes. Blocking antibodies to GDNF inhibit the trophic activity of Schwann cell line-conditioned media by 75%, whereas CT-1 antibodies diminish the myotube-derived activity by 46%. CT-1 and GDNF act synergistically to enhance motoneuron survival in vitro. In vivo, individual motoneurons coexpress both GDNF and CT-1 receptor components. GDNF and CT-1, therefore, are major components of the trophic support provided by the Schwann and muscle cells, respectively. The possibility that they act together on individual motoneurons suggests that the motoneuron must integrate distinct signals from different cellular partners when deciding whether to die or to survive.

SUBMITTER: Arce V

PROVIDER: S-EPMC6792716 | biostudies-literature | 1998 Feb

REPOSITORIES: biostudies-literature

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Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1).

Arce V V Pollock R A RA Philippe J M JM Pennica D D Henderson C E CE deLapeyrière O O

The Journal of neuroscience : the official journal of the Society for Neuroscience 19980201 4

The survival of central neurons depends on multiple neurotrophic factors produced by different cell types. We demonstrate that media conditioned by muscle and Schwann cell lines show strong synergistic effects on survival of purified embryonic day 14.5 rat motoneurons in culture. Different lines of evidence implicate glial cell line-derived neurotrophic factor (GDNF) and cardiotrophin-1 (CT-1) in this synergy. Their expression in the environment of the motoneuron is compartmentalized: gdnf trans ...[more]

PMID: 9454853

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Project description:BackgroundBody composition can be accurately quantified based on computed tomography (CT) and typically reflects an individual's overall health status. However, there is a dearth of research examining the relationship between body composition and survival following esophagectomy.MethodsWe created a cohort consisting of 183 patients who underwent esophagectomy for esophageal cancer without neoadjuvant therapy. The cohort included preoperative PET-CT scans, along with pathologic and clinical data, which were collected prospectively. Radiomic, tumor, PET, and body composition features were automatically extracted from the images. Cox regression models were utilized to identify variables associated with survival. Logistic regression and machine learning models were developed to predict one-, three-, and five-year survival rates. Model performance was evaluated based on the area under the receiver operating characteristics curve (ROC/AUC). To test for the statistical significance of the impact of body composition on survival, body composition features were excluded for the best-performing models, and the DeLong test was used.ResultsThe one-year survival model contained 10 variables, including three body composition variables (bone mass, bone density, and visceral adipose tissue (VAT) density), and demonstrated an AUC of 0.817 (95% CI: 0.738-0.897). The three-year survival model incorporated 14 variables, including three body composition variables (intermuscular adipose tissue (IMAT) volume, IMAT mass, and bone mass), with an AUC of 0.693 (95% CI: 0.594-0.792). For the five-year survival model, 10 variables were included, of which two were body composition variables (intramuscular adipose tissue (IMAT) volume and visceral adipose tissue (VAT) mass), with an AUC of 0.861 (95% CI: 0.783-0.938). The one- and five-year survival models exhibited significantly inferior performance when body composition features were not incorporated.ConclusionsBody composition features derived from preoperative CT scans should be considered when predicting survival following esophagectomy.

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Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1).

Publications

Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1).

Similar Datasets

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