Abstract:
:Astrocyte activation is an important feature in many disorders of the central nervous system, including chronic pain conditions. Activation of astrocytes is characterized by a change in morphology, including hypertrophy and increased size of processes, proliferation, and an increased production of proinflammatory mediators. The xanthine derivatives pentoxifylline and propentofylline are commonly used experimentally as glial inhibitors. These compounds are generally believed to attenuate glial activity by raising cyclic AMP (cAMP) levels and inhibiting glial tumor necrosis factor (TNF) production. In the present study, we show that these substances inhibit TNF and serum-induced astrocyte proliferation and signaling through the mammalian target of rapamycin (mTOR) pathway, demonstrated by decreased levels of phosphorylated S6 kinase (S6K), commonly used as a marker of mTOR complex (mTORC) activation. Furthermore, we show that pentoxifylline and propentofylline also inhibit JNK and p38, but not ERK, activation induced by TNF. In addition, the JNK antagonist SP600125, but not the p38 inhibitor SB203580, prevents TNF-induced activation of S6 kinase, suggesting that pentoxifylline and propentofylline may regulate mTORC activity in spinal astrocytes partially through inhibition of the JNK pathway. Our results suggest that pentoxifylline and propentofylline inhibit astrocyte activity in a broad fashion by attenuating flux through specific pathways.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Norsted Gregory E,Delaney A,Abdelmoaty S,Bas DB,Codeluppi S,Wigerblad G,Svensson CIdoi
10.1002/jnr.23144subject
Has Abstractpub_date
2013-02-01 00:00:00pages
300-12issue
2eissn
0360-4012issn
1097-4547journal_volume
91pub_type
杂志文章abstract::Contrary to widely held beliefs, the gene encoding proteolipid protein (PLP), the major structural protein of central nervous system myelin, is expressed in Schwann cells and their tumors. Proteolipid mRNA was identified in human acoustic neuromas and in rat and rabbit sciatic nerves using a human PLP cDNA as a probe....
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490180402
更新日期:1987-01-01 00:00:00
abstract::Cytoskeletal structures under the cell membrane carry out pivotal roles in the maintenance and remodeling of the cell structures. Reforming of the cytoskeletal networks after partial extraction of membrane components could be a good clue to identify molecular components pertaining the interaction of cytoskeleton with ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20555
更新日期:2005-07-15 00:00:00
abstract::Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA)-differentiated SH-SY5Y cells were examined. Intracellular levels of TNF mRNA accumulation, as ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.10101
更新日期:2002-01-15 00:00:00
abstract::The growth cone, the motile tip of developing neuronal processes, is considered responsible for the exact guidance of axons and synaptogenesis. High activity of tyrosine kinases in growth cones may contribute to the functions of growth cones. Our previous work revealed that vinculin is one of the endogenous substrates...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490300127
更新日期:1991-09-01 00:00:00
abstract::To elucidate the biological differences in neural phenotype between malignant rhabdoid tumor (MRT) and neuroblastoma cell lines, we examined the expression of solube N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex proteins in MRT cell lines under differentiation induction with 12-...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.10330
更新日期:2002-09-01 00:00:00
abstract::Increase of intracellular [Ca(2+)] evoked by action potentials in a cell can induce long-term synaptic plasticity even without concomitant presynaptic stimulation. We used optical recording of the fluorescence of a Ca(2+)-indicator Oregon Green to investigate whether differences in results obtained with modifications ...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20104
更新日期:2004-05-15 00:00:00
abstract::Individuals who regularly shift their sleep timing, like night and/or shift-workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift-work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, an...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.24741
更新日期:2021-02-01 00:00:00
abstract::The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cell...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20090
更新日期:2004-06-15 00:00:00
abstract::Cultured astrocytes from neonatal rat cerebral hemispheres are depolarized by the excitatory neurotransmitter glutamate. In this study we have used selective agonists of different neuronal glutamate receptor subtypes, namely, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate type, to characterize pharmacologic...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490220307
更新日期:1989-03-01 00:00:00
abstract::Synaptic vesicles were isolated from adult bovine cortical gray matter by differential centrifugation and membrane filtration of a hypoosmotically lysed crude mitochondrial fraction. Vesicle preparations were analyzed for purity by electron microscopy and enzyme assays. Polyacrylamide gel electrophoresis of SDS-solubi...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490030204
更新日期:1977-01-01 00:00:00
abstract::Currently antidepressants take several weeks to be effective, which is one of the main reasons why patients with depression quit therapy. In the present study, we examine the acute and subacute effects of soluble epoxide hydolase (sEH) inhibitor (sEHI), a compound shown to have antidepressant effects, on mice. We foun...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.24080
更新日期:2017-12-01 00:00:00
abstract::Charcot-Marie-Tooth neuropathy type 1A (CMT 1 A) is the most common inherited neuropathy in humans and is mostly caused by a 1.5-Mb tandem duplication of chromosome 17 comprising the gene for the peripheral myelin protein 22-kDa (PMP 22). Although there are numerous studies on the functional role of PMP 22, the mechan...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20601
更新日期:2005-09-15 00:00:00
abstract::This study examined the effect of chronic exposure to ethanol and brain-derived neurotrophic factor (BDNF) on the responsiveness of cerebellar granule cells to gamma-aminobutyric acid (GABA). Cerebellar granule cell cultures were chronically exposed to ethanol (100 mM), BDNF (20 ng/ml), or the combination of ethanol a...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.10694
更新日期:2003-09-01 00:00:00
abstract::Transgenic mice with glial fibrillary acidic protein (GFAP) promoter driven-astrocyte production of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) were used to determine whether the pre-existing production of these cytokines in vivo might modulate the sensitivity of neurons to excitotoxic agents. L...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.10635
更新日期:2003-07-15 00:00:00
abstract::Experiments were conducted with the aid of intracellular microelectrodes to study physiological properties of neuropile glial cells in the central nervous system of the medicinal leech. The results showed significant contributions of both K+ and Cl- ions to the membrane potential. The transmitter substance 5-hydroxytr...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490070108
更新日期:1982-01-01 00:00:00
abstract::Brain injury and neuroinflammation are pathophysiologic contributors to acute and chronic neurologic disorders, which are progressive diseases not fully understood. Mammalian metallothioneins I and II (MT-I&II) have significant neuroprotective functions, but the precise mechanisms underlying these effects are still un...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20790
更新日期:2006-05-01 00:00:00
abstract::With the use of an antiserum directed against the human smooth muscle-associated protein 8 (SMAP8) fragment SMAP8(98-138), Western blot and immunohistochemical studies revealed SMAP8 expression in the rat brain. A band with a molecular size of about 45 kDa was detected in tissues from the rat hypothalamus and a weaker...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21315
更新日期:2007-06-01 00:00:00
abstract::Nociceptive neuronal activation in subcortical regions has not been well investigated in functional magnetic resonance imaging (fMRI) studies. The present report aimed to use the blood oxygenation level-dependent (BOLD) fMRI technique to map nociceptive responses in both subcortical and cortical regions by employing a...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.21638
更新日期:2008-06-01 00:00:00
abstract::Accumulation of beta-amyloid protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD), and Abeta-mediated pathogenesis could result from increased production of Abeta or insufficient Abeta clearance by microglia, astrocytes, or the vascular system. Cell-surface receptors, such as scavenger receptors, mig...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20992
更新日期:2006-09-01 00:00:00
abstract::Nerve growth factor (NGF) is a homodimer that binds to two distinct receptor types, TrkA and p75, to support survival and differentiation of neurons. The high-affinity binding on the cell surface is believed to involve a heteroreceptor complex, but its exact nature is unclear. We developed a heterodimer (heteromutein)...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.23116
更新日期:2012-12-01 00:00:00
abstract::Amyotrophic lateral sclerosis is an age-related neurological disease, characterized by neurofilament (NF) accumulation in primary axons followed by degeneration of motor neurons. To elucidate age-related factors that might lead to pathological NF accumulation, NFs were compared between young and aged rats. Electron mi...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:
更新日期:1999-10-15 00:00:00
abstract::Glucocorticoid hormones affect gene expression directly at the level of transcription via intracellular receptors that translocate to the nucleus in the presence of steroid. In the brain, two types of high-affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II, glucocorticoid r...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490270315
更新日期:1990-11-01 00:00:00
abstract::Accumulating evidence indicates an immunosuppressive role for CD4(+)CD25(+) regulatory T cells (Tregs) in autoimmune diseases. Although an impaired Treg function in patients with relapsing-remitting multiple sclerosis (RR-MS) has been reported recently, no information is available so far about Treg function in the pro...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.20852
更新日期:2006-06-01 00:00:00
abstract::In the non-amyloidogenic pathway, the Alzheimer's amyloid precursor protein (APP) is cleaved within the amyloid-beta domain by alpha-secretase precluding deposition of intact amyloid-beta peptide. The large ectodomain released from the cell surface by the action of alpha-secretase has several neuroprotective propertie...
journal_title:Journal of neuroscience research
pub_type: 杂志文章,评审
doi:10.1002/jnr.10737
更新日期:2003-11-01 00:00:00
abstract::This study demonstrates the ability of proteasome inhibitors (lactacystin, MG 115, MG 132) adenosine diphosphate to induce a time- and dose-dependent increase in poly-ADP-ribosylation (PAR) in the neural PC6 cell line, a subclone of PC12 cells. Elevated levels of PAR contribute to the toxicity associated with impaired...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/1097-4547(20000815)61:4<436::AID-JNR10>3.0
更新日期:2000-08-15 00:00:00
abstract::Persephin (PSP) is the most recently discovered member of the GDNF family of neurotrophic factors. We have used an RT-PCR approach to start addressing the putative functional significance of PSP by determining sites of its synthesis in the neonatal rat brain. Generally, two transcripts were found. Sequence analysis of...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19980815)53:4<494::AID-JNR
更新日期:1998-08-15 00:00:00
abstract::Oligodendrocyte responses in vitro to platelet-derived growth factor (PDGF) include proliferation, survival, migration, and changes in cell morphology and molecular expression. Studies of mixed glial cultures established that astrocytes secrete PDGF; thus astrocytes are considered to be key regulators of oligodendrocy...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4547(19960701)45:1<28::AID-JNR3
更新日期:1996-07-01 00:00:00
abstract::Previous studies from our laboratory suggest that Alzheimer's disease sera contain a repertoire of antibodies to the heavy neurofilament subunit (NF-H) and that a subpopulation of these antibodies bind specifically to epitopes highly enriched in NF-H isolated from the purely cholinergic electromotor neurons of Torpedo...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490290409
更新日期:1991-08-01 00:00:00
abstract::Damage to the lateral nucleus of the septum in the rat resulted in atypical learning to a previously meaningless stimulus. Nonreinforced preexposure to a stimulus normally makes more difficult subsequent use of that stimulus for learning. The effect of this preexposure on learning is termed latent inhibition and was d...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490040309
更新日期:1979-01-01 00:00:00
abstract::Low density dissociated cultures of embryonic rat hippocampal cells were used to study the effects of neurotrophin-3 (NT-3) on neuronal morphogenesis. The results obtained indicate that NT-3 enhances neurite outgrowth and branching; this is a dose-dependent effect, detected in approximately 50% of the neurons, and pre...
journal_title:Journal of neuroscience research
pub_type: 杂志文章
doi:10.1002/jnr.490390212
更新日期:1994-10-01 00:00:00