bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated amphetamine treatment induces neurite outgrowth and enhanced amphetamine‐stimulated dopamine release in rat pheochromocytoma cells (PC12 cells) via a protein kinase C‐ and mitogen activated protein kinase‐dependent mechanism
Authors: Park Yang Hae , Kantor Lana , Guptaroy Bipasha , Zhang Minjia , Wang Kevin K. W. , Gnegy Margaret E. 
Published: July 2010

AbstractRepeated intermittent treatment with amphetamine (AMPH) induces both neurite outgrowth and enhanced AMPH‐stimulated dopamine (DA) release in PC12 cells. We investigated the role of protein kinases in the induction of these AMPH‐mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A (PKA). PKC inhibitors chelerythrine (100 nmand 300 nm), Ro31‐8220 (300 nm) and the MAP kinase kinase inhibitor, PD98059 (30 µm) inhibited the ability of AMPH to elicit both neurite outgrowth and the enhanced AMPH‐stimulated DA release. The direct‐acting PKC activator, 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA, 250 nm) mimicked the ability of AMPH to elicit neurite outgrowth and enhanced DA release. On the contrary, a selective PKA inhibitor, 100 µmRp‐8‐Br‐cAMPS, blocked only the development of AMPH‐stimulated DA release but not the neurite outgrowth. Treatment of the cells with acute AMPH elicited an increase in the activity of PKC and MAP kinase but not PKA. These results demonstrated that AMPH‐induced increases in MAP kinase and PKC are important for induction of both the enhancement in transporter‐mediated DA release and neurite outgrowth but PKA was only required for the enhancement in AMPH‐stimulated DA release. Therefore the mechanisms by which AMPH induces neurite outgrowth and the enhancement in AMPH‐stimulated DA release can be differentiated.
Non‐genomic modulation of dopamine release by bisphenol‐A in PC12 cells
Authors: Yoneda Takashi , Hiroi Toyoko , Osada Mayuko , Asada Akira , Funae Yoshihiko 
Published: July 2010

AbstractAn endocrine disruptor chemical, bisphenol‐A (BPA), is reported to have several short‐term actions in various tissues and/or cells; however, the mechanisms of these actions have not been fully elucidated. We investigated short‐term actions evoked by BPA in pheochromocytoma PC12 cells. BPA elicited dopamine release in PC12 cells in a dose‐dependent manner. A selective N‐type calcium channel antagonist (ω‐conotoxin GVIA) and a ryanodine receptor blocker (ryanodine) inhibited the BPA‐induced dopamine release. The expression of ryanodine receptor mRNA was detected by RT–PCR in PC12 cells. Subsequently, in order to prove whether membrane receptors participate in BPA‐evoked dopamine release, a guanine nucleotide‐binding protein inhibitor [guanosine 5′‐(β‐thio) diphosphate], cyclic AMP antagonist (Rp‐cAMPS) or protein kinase A inhibitor (H7 or H89) was added to PC12 cells prior to BPA‐treatment. All of these agents suppressed BPA‐evoked dopamine release, indicating that multiple signaling pathways may be involved in BPA‐evoked dopamine release in PC12 cells. In conclusion, we demonstrated that BPA induced dopamine release in a non‐genomic manner through guanine nucleotide‐binding protein and N‐type calcium channels. These findings illustrate a novel function of BPA and suggest that exposure to BPA influences the function of dopaminergic neurons.
Glutamate regulates Oct‐2 DNA‐binding activity through α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors in cultured chick Bergmann glia cells
Authors: Méndez J. Alfredo , López‐Bayghen Esther , Rojas Fausto , Hernández María Elena , Ortega Arturo 
Published: July 2010

AbstractIonotropic glutamate receptors in cerebellar Bergmann glial cells are linked to transcriptional regulation and, by these means, are thought to play an important role in plasticity, learning and memory and in several neuropathologies. Within the CNS, the transcription factors of the POU family bind their target DNA sequences after a growth factor‐dependent phosphorylation–dephosphorylation cascade. Exposure of cultured Bergmann glial cells to glutamate leads to a time‐ and dose‐dependent increase in Oct‐2 DNA‐binding activity. The use of specific pharmacological tools established the involvement of Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors. Furthermore, the signaling cascade includes phosphatidyl inositol 3‐kinase as well as protein kinase C activation. Interestingly, transcriptional as well as translational inhibitors abolish the glutamate effect, suggesting a transcriptional up‐regulation of the oct‐2 gene. These data demonstrate that Oct‐2 expression is not restricted to neurons and further strengthen the notion that the glial glutamate receptors participate in the modulation of glutamatergic cerebellar neurotransmission.
Expression and involvement of gicerin, a cell adhesion molecule, in the development of chick optic tectum
Authors: Taira Eiichi , Tsukamoto Yasuhiro , Kohama Keiko , Maeda Mitsuyo , Kiyama Hiroshi , Miki Naomasa 
Published: July 2010

AbstractGicerin is a cell adhesion molecule belonging to the immunoglobulin superfamily. It has both a homophilic binding activity and a heterophilic binding activity to neurite outgrowth factor (NOF) a molecule belonging to the laminin family. We have reported many studies on the heterophilic activity of gicerin and NOF, but the function of its homophilic binding activity in vivo had been unclear. In the retina, gicerin is expressed in retinal ganglion cells only when they extend neurites to the optic tectum. In this report we have found that gicerin is also transiently expressed in the optic tectum during this time. First, cell aggregation assays were used to show that gicerin expressed in the optic tectum displays homophilic binding activity. Then, explant cultures of embryonic day 6 chick optic tectum on gicerin‐Fc chimeric protein‐coated dishes and NOF‐coated dishes were carried out. It was found that gicerin–gicerin homophilic interactions promoted cell migration, whereas heterophilic interactions with NOF induced neurite formation. Furthermore, when anti‐gicerin antibodies were injected in order to examine the effect of gicerin protein in the formation of the tectal layer in ovo, cell migration was strongly inhibited. These data suggest that homophilic interaction of gicerin participates in the migration of neural cells during the layer formation and plays a crucial role in the organization of the optic tectum.
Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with IκBα induction and block of NFκB and iNOS activation
Authors: Dehmer Thomas , Heneka Michael T. , Sastre Magdalena , Dichgans Johannes , Schulz Jörg B. 
Published: July 2010

AbstractInflammation has been implicated in the pathogenesis of Parkinson's disease (PD). In the chronic 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) model of PD, inducible NO synthase (iNOS) derived nitric oxide (NO) is an important mediator of dopaminergic cell death. Ligands of the peroxisome proliferator‐activated receptor (PPAR) exert anti‐inflammatory effects. We here investigated whether pioglitazone, a PPARγ agonist, protected mice from MPTP‐induced dopaminergic cell loss, glial activation, and loss of catecholamines in the striatum. As shown by western blot, PPARγ was expressed in the striatum and the substantia nigra of vehicle‐ and MPTP‐treated mice. Oral administration of 20 mg/(kg day) of pioglitazone protected tyrosine hydroxylase (TH)‐positive substantia nigra neurons from death induced by 5 × 30 mg/kg MPTP. However, the decrease of dopamine in the striatum was only partially prevented. In mice treated with pioglitazone, there were a reduced activation of microglia, reduced induction of iNOS‐positive cells and less glial fibrillary acidic protein positive cells in both striatum and substantia nigra pars compacta. In addition, treatment with pioglitazone almost completely blocked staining of TH‐positive neurons for nitrotyrosine, a marker of NO‐mediated cell damage. Because an increase in inhibitory protein‐κ‐Bα (IκBα) expression and inhibition of translocation of the nuclear factor kappaB (NFκB) subunit p65 to the nucleus in dopaminergic neurons, glial cells and astrocytes correlated with the protective effects of pioglitazone, our results suggest that pioglitazone sequentially acts through PPARγ activation, IκBα induction, block of NFκB activation, iNOS induction and NO‐mediated toxicity. In conclusion, treatment with pioglitazone may offer a treatment opportunity in PD to slow the progression of disease that is mediated by inflammation.
Sphingosine‐1‐phosphate induces proliferation and morphological changes of neural progenitor cells
Authors: Harada Jun , Foley Melissa , Moskowitz Michael A. , Waeber Christian 
Published: July 2010

AbstractSphingosine‐1‐phosphate (S1P) is a lipid mediator that exerts multiple cellular functions through activation of G‐protein‐coupled receptors. Although the role of S1P on angiogenesis is well established, its role in neurogenesis is unknown. We examined the effects of S1P on G‐protein activation in brain sections of rat embryo and on neural progenitor cells in culture. Intense S1P‐stimulated [35S]GTPγS labeling was observed as early as E15 in the neuroepithelium and differentiating fields throughout the brain, suggesting that functional S1P receptors are expressed in brain areas with active neurogenesis. mRNA transcripts for several S1P receptor subtypes (S1P1, S1P2, S1P3 and S1P5) were expressed in neural progenitor cells prepared from embryonic rat hippocampus. S1P induced phosphorylation of extracellular signal‐regulated kinase (ERK) and proliferation of neural progenitor cells as determined by BrdU incorporation in a pertussis toxin‐sensitive manner. These effects were prevented by the ERK signaling inhibitor U0126. S1P augmented telomerase activity in neural progenitor cells with similar potency as that of FGF‐2. Furthermore, S1P induced cell‐cell aggregation. This morphological change was transient and prevented by Y‐27632, an inhibitor of Rho‐associated kinase. These results suggest that S1P plays a pleiotropic role in neurogenesis via pathways involving S1P receptors, MAP kinases and Rho kinase.
Normal levels of tryptophan hydroxylase immunoreactivity in the dorsal raphe of depressed suicide victims
Authors: Bonkale Willy L. , Murdock Shayna , Janosky Janine E. , Austin Mark C. 
Published: July 2010

AbstractA variety of evidence suggests that serotonin neurotransmission is altered in the brain of suicide victims and depressed patients. While numerous post‐mortem studies have investigated serotonin transporters and receptors, few studies have examined the biosynthetic integrity of the rate‐limiting enzyme, tryptophan hydroxylase (TPH), in post‐mortem specimens of depressed suicide subjects. Therefore, the aim of the present study was to test the hypothesis that the levels of TPH immunoreactivity (IR) are altered in specific subnuclei of the dorsal raphe (DR) in depressed suicide victims. Suicide victims with a confirmed diagnosis of major depression were matched with non‐psychiatric controls based on age, gender and post‐mortem interval. Frozen tissue sections containing the DR were selected from two anatomical levels and processed for TPH radioimmunocytochemistry. The optical density corresponding to the regional levels of TPH‐IR was quantified in specific subnuclei of the DR from the film autoradiographic images. No significant differences in the levels of TPH‐IR were found in any DR subnuclei between depressed suicide victims and control subjects. The lack of change in TPH‐IR levels does not necessarily imply that serotonin synthesis or neurotransmission is not altered in the brain of depressed subjects. Many factors influence and regulate serotonin synthesis, and it is conceivable that alterations exist at other levels of regulation of serotonin biosynthesis in depression. Our findings indicate that TPH biosynthesis, at least at the protein level, is not significantly altered in the DR of depressed suicide victims.
Role of reactive oxygen species in LPS‐induced production of prostaglandin E2in microglia
Authors: Wang Tongguang , Qin Liya , Liu Bin , Liu Yuxin , Wilson Belinda , Eling Thomas E. , Langenbach Robert , Taniura Seijiro , Hong Jau‐Shyong 
Published: July 2010

AbstractWe determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase‐2 (COX‐2) and the production of prostaglandin E2(PGE2) in lipopolysaccharide (LPS)‐activated microglia. LPS treatment increased intracellular ROS in rat microglia dose‐dependently. Pre‐treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS‐induced release in PGE2. Diphenylene iodonium (DPI), a non‐specific NADPH oxidase inhibitor, decreased LPS‐induced PGE2production. In addition, microglia from NADPH oxidase‐deficient mice produced less PGE2than those from wild‐type mice following LPS treatment. Furthermore, LPS‐stimulated expression of COX‐2 (determined by RT‐PCR analysis of COX‐2 mRNA and western blot for its protein) was significantly reduced by pre‐treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX‐2 expression and PGE2production. As a comparison, scavenging ROS had no effect on LPS‐induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX‐2 and the subsequent production of PGE2during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX‐2 expression and PGE2production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation‐mediated neurodegenerative diseases.
Microarray analysis of gene expression on herbal glycoside recipes improving deficient ability of spatial learning memory in ischemic mice
Authors: Wang Zhong , Du Qingyou , Wang Fusheng , Liu Zhongrong , Li Baigang , Wang Anmin , Wang Yongyan 
Published: July 2010

AbstractIn order to reveal the mechanism of herbal glycoside recipes retrieving deficient ability of spatial learning memory in mice suffering from cerebral ischemia/reperfusion, a microarray system was used to analyze gene expression in those groups with increasing ability of spatial learning memory who were different from ischemic mice. In this work, we reported a comprehensive characterization of gene expression profiles of mouse hippocampus by the use of cDNA microarray system containing 1176 known genes in middle cerebral artery occlusion (MCAO) ischemic mice after treating with different dosage recipes of glycoside herbs (30, 90, and 270 mg/kg). The ability of spatial learning memory in ischemic mice was found to be decreased. The pathological process in ischemic mouse brain showed that a complex related to 100 genes' expression yielded 1.8‐fold. Dose‐dependent effects showed an improvement in the deficient ability and reduction in infarct volume when treated with glycoside recipes. Many genes (38–46) in expression were found greater than 1.8‐fold in those effective recipes groups, including genes in cell cycle regulation, signal transduction, nerve system transcription factors, DNA binding protein, etc. Nine genes related to retrieving deficient ability of spatial learning memory treated with glycoside recipes were also found in this study. These results suggest that microarray analysis of gene expression might be useful for elucidating the mechanisms of pharmacological function of recipes.
Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle
Authors: Kudo Chiho , Wada Koichiro , Masuda Tomotake , Yonemura Toshimitsu , Shibuya Atsuhito , Fujimoto Yohko , Nakajima Atsushi , Niwa Hitoshi , Kamisaki Yoshinori 
Published: July 2010

AbstractEndocrine disruptors (EDs) are a great concern throughout the world, because they have adverse effects on human health and wildlife. In the present study, we investigated the effects of EDs on the proliferation and survival of murine neural stem cells (NSCs). In contrast to bisphenol A, phthalic acid benzyl n‐butyl ester, phthalic acid di‐n‐butyl ester and phthalic acid di(2‐ethylhexyl) ester, the treatment of NSCs with 4‐nonylphenol for 24 h inhibited cell growth in a concentration‐dependent manner. In addition, treatment with 4‐nonylphenol resulted in nuclear condensation and DNA fragmentation (morphological changes due to apoptosis) in NSCs after 12 h of exposure, and activated caspase‐3 after 6 h and 9 h of exposure. Furthermore, an exposure to 4‐nonylphenol led to the accumulation of cells at the G2/M phase interface and down‐regulated the protein levels of cyclin A and B1, which are the major regulatory proteins at the G2to M transition of the cell cycle. Together, these results indicate that, in contrast to other EDs, 4‐nonylphenol may exhibit a potent cytotoxicity through apoptosis via the caspase cascade and cell cycle arrest at the G2/M phase, and suggest that 4‐nonylphenol may affect neurogenesis in the CNS.
Microarray analysis of developmental plasticity in monkey primary visual cortex
Authors: Lachance Pascal E. D. , Chaudhuri Avi 
Published: July 2010

AbstractWe performed microarray gene expression analyses on the visual cortex of Old‐World monkeys (Cercopithicus aethiops) in an effort to identify transcripts associated with developmental maturation and activity‐driven changes during the visual critical period. Samples derived from normal animals and those subjected to monocular enucleation (ME) were hybridized to human Affymetrix HG‐U95Av2 oligonucleotide microarrays (N = 12) and the results were independently validated by real‐time quantitative RT‐PCR. To identify genes exhibiting significant expression differences among our samples, the microarray hybridization data were processed with two software packages that use different analytical models (Affymetrix MicroArray Suite 5.0, dChip 1.2). We identified 108 transcripts within diverse functional categories that differed in their visual cortical expression at the height of the critical period when compared to adults. The expression levels of four transcripts were also globally modulated following ME during the critical period. These transcripts are particularly sensitive to ME during the critical period but are not significantly modulated in ME adults. Three of the ME‐driven genes (NGFI‐B, egr3, NARP) are known immediate‐early genes (IEG) while the other (DUSP6) is a phosphatase that can regulate IEG expression. The putative biological significance of the ME‐driven and developmentally regulated genes is discussed with respect to the critical period for activity‐dependent visual cortical neuroplasticity.
The type 1 interleukin‐1 receptor is essential for multiple aspects of brain inflammation
Authors: Levison S. W. , Basu A. , Krady J. K. , O'Malley M. O. , Styren S. D. , DeKosky S. T. 
Published: July 2010

Interleukin‐1 (IL‐1) is induced immediately after brain imjury and elevated levels of IL‐1 have been strongly implicated in the neurodegeneration that accompanies stroke, Alzheimer's disease and Multiple Sclerosis. Antagonizing IL‐1 reduces cell death; however, the basis for this protection has not been elucidated. Here we analyzed the response to penetrating brain injury in mice lacking the type 1 interleukin receptor (IL‐1R1) to determine which cellular and molecular mediators of tissue damage require IL‐1 signaling. At the cellular level fewer amoeboid microglia/macrophages appeared adjacent to the injured brain tissue in IL‐1R1 null mice, and those microglia present at early postinjury intervals retained their resting morphology. Astrogliosis also was mildly abrogated. At the molecular level, cyclooxygenase 2 and IL‐6 expression were depressed and delayed. Interestingly, basal levels of cyclooxygenase 2, IL‐1 and IL‐6 were significantly lower in the IL‐1R1 null mice. Additionally, stimulation of VCAM‐1 mRNA was depressed in the IL‐1R1 null mice, and correspondingly, there was reduced migration of peripheral macrophages into the IL‐1R1 null brain after injury. This observation correlated with a reduced number of cyclooxygenase 2+ amoeboid phagocytes adjacent to the injury. By contrast, the production of nerve growth factor was only mildly affected. Since antagonizing IL‐1 protects neural cells in experimental models of stroke and multiple sclerosis, our data suggest that cell preservation is achieved by abrogating microglial/macrophage activation and the subsequent self‐propagating cycle of inflammation.Acknowledgements:  Supported by NMSS Award #RG 3837.
Myelin transcription factor 1 function in oligodendrocyte development
Authors: Nielsen J. A. , Hudson L. D. , Armstrong R. C. 
Published: July 2010

Myelin transcription factor 1 (Myt1) is a CCHC zinc‐finger protein that is expressed in oligodendrocyte progenitors (OP) and is down‐regulated as oligodendrocytes differentiate and accumulate proteolipid protein (PLP). Myt1 contains six zinc‐finger DNA‐binding domains, a putative acidic transcriptional activation domain, and an alpha‐helical protein–protein interaction domain. Myt1 has two zinc‐fingers near the N‐terminus and four zinc‐fingers (4F) near the C‐terminus. Each set of zinc‐fingers can bind to the PLP promoter. The objective of this study was to determine the function of Myt1 by expressing the 4F domain of Myt1, which lacks the putative transcriptional activation domain and protein–protein interaction domain. We predicted the 4F domain would compete for Myt1 response elements, and lacking other functional domains would interfere with endogenous Myt1 function. A retroviral expression system that included a FLAG epitope tag was used to ectopically express the 4F domain of Myt1 in cultured rat neonatal OPs. OPs and their progeny exhibited nuclear immunoreactivity for the 4F‐FLAG fusion protein. Expression of 4F in OPs grown with PDGF and FGF mitogens reduced proliferation as compared to controls. In the absence of mitogens, expression of 4F inhibited the differentiation of OPs as assessed by morphological criteria, O1 immunostaining, and PLP mRNA expression. This 4F inhibition of OP differentiation along the oligodendrocyte pathway was not due to alternative differentiation along an astrocytic pathway. These data suggest that Myt1 regulates a critical transition in oligodendrocyte lineage development in modulating the OP proliferative response relative to terminal differentiation and myelin gene expression.Acknowledgements: Supported by USUHS grant RO70IE.
CNTF is up‐regulated in astrocytes during spinal cord remyelination and stimulates FGF‐2 production
Authors: Levison S. W. , Albrecht P. J. , Murtie J. C. , Ness J. K. , Redwine J. M. , Armstrong R. C. 
Published: July 2010

FGF‐2 is a potent mitogen and survival factor for oligodendrocyte progenitors in vitro, and it is induced in astrocytes in conjunction with successful remyelination during recovery from murine hepatitis virus (MHV) induced spinal cord demyelination. However, the factor(s) responsible for inducing FGF‐2 after demyelination in astrocytes are unknown. Here we used in vivo and in vitro paradigms to assess whether ciliary neurotrophic factor (CNTF) could be responsible for FGF‐2 induction during remyelination. In mice recovering from MHV‐induced demyelination, increased CNTF expression coincided with spinal cord remyelination. Immunohistochemistry demonstrated that CNTF protein was present within astrocytes surrounding and within remyelinating lesions. After directly injecting CNTF into the spinal cord, FGF‐2 mRNA increased in spinal cord astrocytes. Furthermore, CNTF induced FGF‐2 mRNA over 2.5 fold in cultured mouse spinal cord astrocytes as determined by kinetic RT–PCR analysis. Although IL‐1β has been implicated in FGF‐2 production, IL‐1β mRNA was not detected during remyelination, nor did IL‐1β induce FGF‐2 mRNA from mouse spinal cord astrocytes in vitro. Altogether, these results strongly implicate CNTF as an upstream positive regulator of FGF‐2 production in astrocytes during early remyelination.Acknowledgements:  Supported by NMSS Award #RG 3837 (SWL) and NS 33316 (RCA).