Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons

Katsuki, Hiroshi; Itsukaichi, Yuko; Matsuki, Norio

doi:10.1016/s0006-8993(00)02953-x

Cited by 16 publications

(12 citation statements)

References 43 publications

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“…SUN11602 also induced neurite outgrowth of the primarily cultured hippocampal neurons, consistent with the knowledge that bFGF accelerates neurite outgrowth and branching of cultured hippocampal neurons (Ikegaya et al, 2000;Katsuki et al, 2000). It has been reported that transgenic mice overexpressing human amyloid precursor protein do not show any significant neuronal cell loss, despite large accumulations of fibrillar Aβ (Games et al, 1995;Hsiao et al, 1996).…”

Section: Discussionsupporting

confidence: 86%

SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer׳s disease induced by amyloid β and excitatory amino acids

Ogino¹,

Murayama²,

Noshita³

et al. 2014

Brain Research

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Basic fibroblast growth factor (bFGF/FGF-2) is known to possess neuroprotective and neurite outgrowth activity properties. In this study, the effects of a novel synthetic compound that mimics the neuroprotective properties of bFGF - SUN11602 - were examined in vitro and in vivo. SUN11602 promoted neurite outgrowth of primarily cultured rat hippocampal neurons. For the in vivo study, an Alzheimer's disease (AD) model with severe damage to the hippocampal tissue was constructed by injecting the hippocampi of rats with aggregated Aβ1-40, followed 48 h later by an injection of ibotenate [an agonist for N-methyl-d-aspartate (NMDA) receptor]. Oral administration of SUN11602 at the midpoint of Aβ1-40 and ibotenate injections attenuated short-term memory impairment in the Y-maze test, as well as spatial learning deficits in the water maze task. In addition, the SUN11602 treatment inhibited the increase of peripheral-type benzodiazepine-binding sites (PTBBS), which are a marker for gliosis. A negative correlation was found between PTBBS numbers and learning capacity in the water maze task. These results suggest that SUN111602 improved memory and learning deficits in the hippocampally lesioned rats by preventing neuronal death and/or promotion of neurite outgrowth. Taken together, these results indicate that SUN11602, a bFGF-like compound with neuroprotective and neurite outgrowth activity, may be beneficial for the treatment of progressive neurodegenerative diseases such as AD.

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Section: Discussionsupporting

confidence: 86%

SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer׳s disease induced by amyloid β and excitatory amino acids

Ogino¹,

Murayama²,

Noshita³

et al. 2014

Brain Research

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“…Cultured hippocampal neurons express receptors for other trophic factors, including IGF-1 [58], [59] and bFGF [60], [61], which activate the same BDNF-induced signaling pathways in cultured hippocampal neurons. Moreover, IGF-I enhances the expression of TrkB receptors and the ability of BDNF to induce ERK1/2 phosphorylation in cerebrocortical neurons [62] while bFGF rapidly stimulates BDNF expression in the hippocampal cell line HiB5 [63].…”

Section: Resultsmentioning

confidence: 99%

BDNF Regulates the Expression and Distribution of Vesicular Glutamate Transporters in Cultured Hippocampal Neurons

et al. 2013

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BDNF is a pro-survival protein involved in neuronal development and synaptic plasticity. BDNF strengthens excitatory synapses and contributes to LTP, presynaptically, through enhancement of glutamate release, and postsynaptically, via phosphorylation of neurotransmitter receptors, modulation of receptor traffic and activation of the translation machinery. We examined whether BDNF upregulated vesicular glutamate receptor (VGLUT) 1 and 2 expression, which would partly account for the increased glutamate release in LTP. Cultured rat hippocampal neurons were incubated with 100 ng/ml BDNF, for different periods of time, and VGLUT gene and protein expression were assessed by real-time PCR and immunoblotting, respectively. At DIV7, exogenous application of BDNF rapidly increased VGLUT2 mRNA and protein levels, in a dose-dependent manner. VGLUT1 expression also increased but only transiently. However, at DIV14, BDNF stably increased VGLUT1 expression, whilst VGLUT2 levels remained low. Transcription inhibition with actinomycin-D or α-amanitine, and translation inhibition with emetine or anisomycin, fully blocked BDNF-induced VGLUT upregulation. Fluorescence microscopy imaging showed that BDNF stimulation upregulates the number, integrated density and intensity of VGLUT1 and VGLUT2 puncta in neurites of cultured hippocampal neurons (DIV7), indicating that the neurotrophin also affects the subcellular distribution of the transporter in developing neurons. Increased VGLUT1 somatic signals were also found 3 h after stimulation with BDNF, further suggesting an increased de novo transcription and translation. BDNF regulation of VGLUT expression was specifically mediated by BDNF, as no effect was found upon application of IGF-1 or bFGF, which activate other receptor tyrosine kinases. Moreover, inhibition of TrkB receptors with K252a and PLCγ signaling with U-73122 precluded BDNF-induced VGLUT upregulation. Hippocampal neurons express both isoforms during embryonic and neonatal development in contrast to adult tissue expressing only VGLUT1. These results suggest that BDNF regulates VGLUT expression during development and its effect on VGLUT1 may contribute to enhance glutamate release in LTP.

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“…In in vitro studies, the induction of proliferation activities by bFGF in various types of cells, including vascular cells (10,11,16), and the antiapoptotic action of bFGF on neural cells (14) have been reported. In in vivo studies, the effects of bFGF have been investigated in the fields of central and peripheral nervous systems (27)(28)(29)(30), skin (17), bone (18,19), heart (22,23), and vasculatures (20,21), and beneficial effects have been reported both experimentally and clinically. In addition to these effects, bFGF induces NO production through endothelial NO synthase activation, resulting in vasodilation (12,13,38).…”

Section: Discussionmentioning

confidence: 99%

“…The half-life time of bFGF is relatively short (24), and cross-linked gelatin hydrogel (CGH) has been used to maintain the bioactivity of locally administered bFGF for an extended period (25,26). Furthermore, it has been reported that bFGF has effects on the central nervous system (27,28) and peripheral nervous system (29,30). However, the effects of bFGF on diabetic neuropathy have not been investigated.…”

mentioning

confidence: 99%

Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in Rats

et al. 2006

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Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.

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Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons

Cited by 16 publications

References 43 publications

SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer׳s disease induced by amyloid β and excitatory amino acids

SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer׳s disease induced by amyloid β and excitatory amino acids

BDNF Regulates the Expression and Distribution of Vesicular Glutamate Transporters in Cultured Hippocampal Neurons

Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in Rats

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