Levels of transforming growth factor alpha (TGF‐a)in human cerebrospinal fluid

Setten, G.‐B. van; Edström, Lars; Stibler, Helena; Rasmussen, S; Schultz, Gregory S.

doi:10.1016/s0736-5748(98)00069-0

Cited by 19 publications

(8 citation statements)

References 14 publications

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“…BMP7 [24], TGFb1 and 2 [25][26][27][28][29], PDGF-BB [30], NGF [31] FGF-2 [32,33] and TGF-a [34] have all been identified. Only in a few circumstances are their effects on leptomeningeal cells known.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

et al. 2011

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The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1-STAT3, MEK1-p44/42MAPK, Akt-mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from "normal" volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

et al. 2011

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“…That is, infusions of TGF-α or EGF into the third ventricle near the SCN suppressed activity and food consumption and cause weight loss [42]. The SCN could communicate with other areas around the third ventricle via the cerebrospinal fluid; the SCN is known to release at least one peptide into cerebrospinal fluid (vasopressin) [40] and TGF-α has been measured in human cerebrospinal fluid [46]. In addition, EGF receptors, localized by immunohistochemistry or by in situ hybridization, have been reported in hypothalamic areas around the third ventricle [25, 26].…”

Section: Discussionmentioning

confidence: 99%

Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters

Gilbert¹,

Davis²

2009

Behavioural Brain Research

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The growth factor, transforming growth factor-alpha (TGF-α) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-α is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-α suppresses activity. TGF-α suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-α is correlated with some cancers, and it is possible the TGF-α and its receptor, the epidermal growth factor receptor (EGFR), mediate fatigue and weight loss associated with cancer. If true for cancers outside of the brain, then systemic TGF-α should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-α. Both treatments suppressed activity and infusions caused reduced food consumption and weight loss. To identify areas of the brain that might mediate these effects of systemic TGF-α, we used immunohistochemistry to localize cells with an activated MAP kinase signaling pathway (phosphorylated ERK1). Cells were activated in two hypothalamic areas, the paraventricular nucleus and a narrow region surrounding the third ventricle. These sites could be targets of TGF-α produced in the SCN but could also mediate effects of elevated TGF-α from tumors both within and outside the central nervous system.

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“…Growth factors such as EGF, FGFb, transforming growth factor‐α (TGF‐α), nerve growth factor (NGF) (Craig et al,1996), insulin‐like growth factor 1 (IGF1) (Pérez‐Martin et al,2003), brain‐derived neurotrophic factor (BDNF) (Goldman,1995), and ciliary neurotrophic factor (CNTF) (Kokoeva et al,2005) have been reported to stimulate in vivo or in vitro adult neurogenesis. Most of them have been reported to be present in the CSF (Van Setten et al,1999; Albrecht et al,2006; Bilic et al,2006). The possibility exists that ependymal cells control access of growth factors from the CSF to the subependyma (cf.…”

Section: Discussionmentioning

confidence: 99%

Neuroblast proliferation on the surface of the adult rat striatal wall after focal ependymal loss by intracerebroventricular injection of neuraminidase

Gómez-Roldán¹,

Pérez‐Martín²,

Capilla-González

et al. 2008

J of Comparative Neurology

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The subventricular zone of the striatal wall of adult rodents is an active neurogenic region for life. Cubic multiciliated ependyma separates the subventricular zone from the cerebrospinal fluid (CSF) and is involved in the control of adult neurogenesis. By injecting neuraminidase from Clostridium perfringens into the right lateral ventricle of the rat, we provoked a partial detachment of the ependyma in the striatal wall. The contralateral ventricle was never affected and was used as the experimental control. Neuraminidase caused widening of the intercellular spaces among some ependymal cells and their subsequent detachment and disintegration in the CSF. Partial ependymal denudation was followed by infiltration of the CSF with macrophages and neutrophils from the local choroid plexus, which ependymal cells never detached after neuraminidase administration. Inflammation extended toward the periventricular parenchyma. The ependymal cells that did not detach and remained in the ventricle wall never proliferated. The lost ependyma was never recovered, and ependymal cells never behaved as neural stem cells. Instead, a scar formed by overlapping astrocytic processes sealed those regions devoid of ependyma. Some ependymal cells at the border of the denudated areas lost contact with the ventricle and became located under the glial layer. Concomitantly with scar formation, some subependymal cells protruded toward the ventricle through the ependymal breaks, proliferated, and formed clusters of rounded ventricular cells that expressed the phenotype of neuroblasts. Ventricular clusters of neuroblasts remained in the ventricle up to 90 days after injection. In the subventricular zone, adult neurogenesis persisted.

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Levels of transforming growth factor alpha (TGF‐a)in human cerebrospinal fluid

Cited by 19 publications

References 14 publications

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters

Neuroblast proliferation on the surface of the adult rat striatal wall after focal ependymal loss by intracerebroventricular injection of neuraminidase

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