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Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro.

Boato F, Hechler D, Rosenberger K, Lüdecke D, Peters EM, Nitsch R, Hendrix S - J Neuroinflammation (2011)

Bottom Line: We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4.Surprisingly, a similar increase of neurite growth was induced by IL-1β.Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Functional Morphology & BIOMED Institute, Hasselt University, Belgium.

ABSTRACT
Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices.

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NT-3 and IL-1beta do not increase neurite outgrowth of transverse spinal cord slices. A: Transverse spinal cord slices were prepared from E13 spinal cords and the ratio between neurite area and slice area were compared. B: representative photomicrograph showing the increase in outgrowth of NGF treated EC compared to control. NGF (500 ng/ml) serves as positive control. C: NT-3 and IL-1β (500 ng/ml) were added to the culture medium of organotypic transverse spinal cord slices. Only NGF significantly increases neurite density, while NT-3, IL-1β or a combination of these factors does not influence neurite outgrowth. n = 9-11 slices. *: Statistically significant difference to control; p < 0.05 (Mann Whitney U test). Arrow heads indicate outgrowing neuritis. Scale bar: 50 μm.
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Figure 3: NT-3 and IL-1beta do not increase neurite outgrowth of transverse spinal cord slices. A: Transverse spinal cord slices were prepared from E13 spinal cords and the ratio between neurite area and slice area were compared. B: representative photomicrograph showing the increase in outgrowth of NGF treated EC compared to control. NGF (500 ng/ml) serves as positive control. C: NT-3 and IL-1β (500 ng/ml) were added to the culture medium of organotypic transverse spinal cord slices. Only NGF significantly increases neurite density, while NT-3, IL-1β or a combination of these factors does not influence neurite outgrowth. n = 9-11 slices. *: Statistically significant difference to control; p < 0.05 (Mann Whitney U test). Arrow heads indicate outgrowing neuritis. Scale bar: 50 μm.

Mentions: In order to investigate potential differences between the effects of IL-1β and NT-3 on cerebral and spinal cord neurites, we further analyzed both factors in a model of organotypic transverse spinal cord slices (Figure 3). Spinal cord slices were embedded in a collagen matrix similar to the brain slice model and the ratio between outgrowth area and slice size was determined (Figure 3A, see materials & methods section for details). Surprisingly, the application of 500 ng/ml of NT-3 or IL-1β as well as the combined application of both factors at the same concentration, had no effect on the outgrowth ratio compared to control slices, suggesting a cortex-specific effect of both factors (Figure 3C). As a positive control for the model we used 500 ng/ml of NGF, which significantly stimulated the outgrowth ratio of transverse spinal cord slices compared to untreated controls (Figure 3B, C).


Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro.

Boato F, Hechler D, Rosenberger K, Lüdecke D, Peters EM, Nitsch R, Hendrix S - J Neuroinflammation (2011)

NT-3 and IL-1beta do not increase neurite outgrowth of transverse spinal cord slices. A: Transverse spinal cord slices were prepared from E13 spinal cords and the ratio between neurite area and slice area were compared. B: representative photomicrograph showing the increase in outgrowth of NGF treated EC compared to control. NGF (500 ng/ml) serves as positive control. C: NT-3 and IL-1β (500 ng/ml) were added to the culture medium of organotypic transverse spinal cord slices. Only NGF significantly increases neurite density, while NT-3, IL-1β or a combination of these factors does not influence neurite outgrowth. n = 9-11 slices. *: Statistically significant difference to control; p < 0.05 (Mann Whitney U test). Arrow heads indicate outgrowing neuritis. Scale bar: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275552&req=5

Figure 3: NT-3 and IL-1beta do not increase neurite outgrowth of transverse spinal cord slices. A: Transverse spinal cord slices were prepared from E13 spinal cords and the ratio between neurite area and slice area were compared. B: representative photomicrograph showing the increase in outgrowth of NGF treated EC compared to control. NGF (500 ng/ml) serves as positive control. C: NT-3 and IL-1β (500 ng/ml) were added to the culture medium of organotypic transverse spinal cord slices. Only NGF significantly increases neurite density, while NT-3, IL-1β or a combination of these factors does not influence neurite outgrowth. n = 9-11 slices. *: Statistically significant difference to control; p < 0.05 (Mann Whitney U test). Arrow heads indicate outgrowing neuritis. Scale bar: 50 μm.
Mentions: In order to investigate potential differences between the effects of IL-1β and NT-3 on cerebral and spinal cord neurites, we further analyzed both factors in a model of organotypic transverse spinal cord slices (Figure 3). Spinal cord slices were embedded in a collagen matrix similar to the brain slice model and the ratio between outgrowth area and slice size was determined (Figure 3A, see materials & methods section for details). Surprisingly, the application of 500 ng/ml of NT-3 or IL-1β as well as the combined application of both factors at the same concentration, had no effect on the outgrowth ratio compared to control slices, suggesting a cortex-specific effect of both factors (Figure 3C). As a positive control for the model we used 500 ng/ml of NGF, which significantly stimulated the outgrowth ratio of transverse spinal cord slices compared to untreated controls (Figure 3B, C).

Bottom Line: We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4.Surprisingly, a similar increase of neurite growth was induced by IL-1β.Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Functional Morphology & BIOMED Institute, Hasselt University, Belgium.

ABSTRACT
Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices.

Show MeSH
Related in: MedlinePlus