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Neurotrophic Effects (neurotrophic + effects)
Selected AbstractsComparison of the growth hormone, IGF-1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controlsEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2006E. Bilic Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased (P = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development. [source] Neurotrophic effects of GM1 ganglioside and electrical stimulation on cochlear spiral ganglion neurons in cats deafened as neonatesTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007Patricia A. Leake Abstract Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al. [1999] J Comp Neurol 412:543,562). However, electrical stimulation only partially prevents SG degeneration after deafening and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries, and Alzheimer's disease. GM1 activates trkB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafened as neonates and received daily injections of GM1, beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation. GM1-treated and deafened control groups were examined at 7,8 weeks of age; additional GM1 and no-GM1 deafened control groups received a cochlear implant at 7,8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the no-GM1 group as compared to the contralateral, nonstimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation. J. Comp. Neurol. 501:837,853, 2007. © 2007 Wiley-Liss, Inc. [source] Pigment epithelium-derived factor induces the production of chemokines by rat microgliaGLIA, Issue 4 2005Asako Takanohashi Abstract Many studies have shown that pigment epithelium-derived factor (PEDF) has neurotrophic effects on retinal cells and hippocampal, spinal cord, and cerebellar granule cell neurons, but much less work has examined the effects of PEDF on glia. In this study, we show that PEDF changes microglial morphology within 1 h of exposure, to a more deactivated form, while having no effect on the expression of such activation markers as OX-42 and ED-1. In contrast, urea activates acid phosphatase, and PEDF blocks that activation. PEDF also activates NF,B, accompanied by the induction of mRNAs and proteins for the chemokines macrophage inflammatory protein-1, (MIP-1,, MIP-2, and MIP-3,. All the chemokines stimulate acid phosphatase activity, and high doses of MIP-2 and MIP-3,), alter the morphology of the microglia at 1 h after treatment. These results suggest that the use of PEDF for clinical treatments, such as for retinal neovascularization, brain injury, or ischemia, should be undertaken with caution because of the possibility of induction of inflammation caused by microglial or other immune cell migration in response to the chemokines induced by PEDF. © 2005 Wiley-Liss, Inc. [source] Epidermal Growth Factor Induces Oxidative Neuronal Injury in Cortical CultureJOURNAL OF NEUROCHEMISTRY, Issue 1 2000Yoo Kyung Cha Abstract : Recently, we have demonstrated that certain neurotrophic factors can induce oxidative neuronal necrosis by acting at the cognate tyrosine kinase-linked receptors. Epidermal growth factor (EGF) has neurotrophic effects via the tyrosine kinase-linked EGF receptor (EGFR), but its neurotoxic potential has not been studied. Here, we examined this possibility in mouse cortical culture. Exposure of cortical cultures to 1-100 ng/ml EGF induced gradually developing neuronal death, which was complete in 48-72 h ; no injury to astrocytes was noted. Electron microscopic findings of EGF-induced neuronal death were consistent with necrosis ; severe mitochondrial swelling and disruption of cytoplasmic membrane occurred, whereas nuclei appeared relatively intact. The EGF-induced neuronal death was accompanied by increased free radical generation and blocked by the anti-oxidant Trolox. Suggesting mediation by the EGFR, an EGFR tyrosine kinase-specific inhibitor, C56, attenuated EGF-induced neuronal death. In addition, inhibitors of extracellular signal-regulated protein kinase 1/2 (Erk-1/2) (PD98056), protein kinase A (H89), and protein kinase C (GF109203X) blocked EGF-induced neuronal death. A p38 mitogen-activated protein kinase inhibitor (SB203580) or glutamate antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) showed no protective effect. The present results suggest that prolonged activation of the EGFR may trigger oxidative neuronal injury in central neurons. [source] Adipocyte-derived angiopoietin-1 supports neurite outgrowth and synaptogenesis of sensory neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Joanna Kosacka Abstract Sensory and sympathetic innervation of the white fat tissue (WAT) contributes to lipolysis. In addition, both fiber types adapt in density to weight gain and loss. Because these findings are indicative for a tight control of nerve fiber plasticity by adipokines, we tested whether adipocytes control neurite growth of sensory neurons through angiopoietin-1 (Ang-1). We further considered initial hints that Ang-1-induced neuritogenesis involves transactivation of the high-affinity nerve growth factor (NGF) receptor trkA. Coculturing dorsal root ganglion (DRG) cells with 3T3-L1 adipocytes supported neurite outgrowth. These neurotrophic effects were associated with the increased expression of Ang-1 (presumably in adipocytes) as well as of trkA. The effects were abolished upon inactivating Ang-1 in culture with selective antibodies. Likewise, neurite outgrowth was impaired in the presence of inactivating NGF antibodies as well as upon inhibition of the NGF high-affinity trkA receptor with the antagonist K252a, indicating a tight cooperation of Ang-1 and NGF in the control of neuritogenesis. DRG-adipipocyte cocultures were further used to establish whether sensory neurons would form synaptic contacts with adipocytes. Electron microscopy demonstrated that cultured sensory neurons develop predominantly neuroneuronal synapses but seem to affect adipocytes by synapses en passant. Comparably to the case for neuritogenesis, expression of the presynaptic protein synaptophysin as well of the postsynaptic protein PSD-95 correlated with Ang-1 levels in culture. It is concluded that adipocyte-secreted Ang-1 supports neurite outgrowth, which is involved in synaptogenesis. The novel function of Ang-1 appears to play a physiological role in WAT plasticity. © 2006 Wiley-Liss, Inc. [source] Molecular targets of lithium actionACTA NEUROPSYCHIATRICA, Issue 6 2003B Corbella Lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. However, the precise mechanism of lithium action is not yet well understood. Extensive research aiming to elucidate the molecular mechanisms underlying the therapeutic effects of lithium has revealed several possible targets. The behavioral and physiological manifestations of the illness are complex and are mediated by a network of interconnected neurotransmitter pathways. Thus, lithium's ability to modulate the release of serotonin at presynaptic sites and modulate receptor-mediated supersensitivity in the brain remains a relevant line of investigation. However, it is at the molecular level that some of the most exciting advances in the understanding of the long-term therapeutic action of lithium will continue in the coming years. The lithium cation possesses the selective ability, at clinically relevant concentrations, to alter the PI second-messenger system, potentially altering the activity and dynamic regulation of receptors that are coupled to this intracellular response. Subtypes of muscarinic receptors in the limbic system may represent particularly sensitive targets in this regard. Likewise, preclinical data have shown that lithium regulates arachidonic acid and the protein kinase C signaling cascades. It also indirectly regulates a number of factors involved in cell survival pathways, including cAMP response element binding protein, brain-derived neurotrophic factor, bcl-2 and mitogen-activated protein kinases, and may thus bring about delayed long-term beneficial effects via under-appreciated neurotrophic effects. Identification of the molecular targets for lithium in the brain could lead to the elucidation of the pathophysiology of bipolar disorder and the discovery of a new generation of mood stabilizers, which in turn may lead to improvements in the long-term outcome of this devastating illness (1). [source] | |||||||||||||