bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction and microglia activation in the murine running wheel model
Authors: Olah Marta , Ping Gao , De Haas Alexander H. , Brouwer Nieske , Meerlo Peter , Van Der Zee Eddy A. , Biber Knut , Boddeke Hendrikus W. G. M. 
Published: December 2008

AbstractRecently, activated microglia have been shown to be involved in the regulation of several aspects of neurogenesis under certain experimental conditions both in vitro and in vivo. A neurogenesis supportive microglia phenotype has been suggested to arise from the interaction of microglia with homing encephalitogenic T cells. However, a unified hypothesis regarding the exact nature of microglia activity that is supportive of neurogenesis is yet missing from the field. Our aim was to investigate the connection between microglia activity and adult hippocampal neurogenesis under physiological conditions. To address this question we compared the level of microglia activation in the hippocampus of mice, which had access to a running wheel for 10 days and that of sedentary controls. Suprisingly, despite elevated levels of proliferation of neural precursors and survival of newborn neurons in the dentate gyrus microglia remained in a “resting” state morphologically, antigenically, and at the transcriptional level. Moreover, neither T cells nor MHCII expressing microglia were present in the hippocampal brain parenchyma. Though microglia in the dentate gyrus of the runners proliferated at a higher level than in the sedentary controls, this difference was also present in non‐neurogenic sites. Therefore, our findings suggest that classical signs of microglia activation and microglia activation arising from interaction with T cells in particular are not a prerequisite for the activity‐induced increase in adult hippocampal neurogenesis in C57Bl/6 mice. Thus, our results draw attention on the species and model differences that might exist regarding the regulation of adult hippocampal neurogenesis. © 2008 Wiley‐Liss, Inc.
Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I alters oligodendrocyte turnover in the corpus callosum
Authors: Hua Kun , Forbes M. Elizabeth , Lichtenwalner Robin J. , Sonntag William E. , Riddle David R. 
Published: December 2008

AbstractGrowth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF‐I axis on adult neurogenesis, but it is unclear whether the GH/IGF‐I axis influences glial turnover in the normal adult brain. In the current study, we used a selective model of adult‐onset GH and IGF‐I deficiency to evaluate the role of GH and IGF‐I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF‐I‐deficient dwarf rats of the Lewis strain were made GH/IGF‐I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF‐I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult‐onset GH/IGF‐I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging‐related changes in the GH/IGF‐I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging‐related cognitive changes and deficits in remyelination after injury. © 2008 Wiley‐Liss, Inc.
Sodium channel activity modulates multiple functions in microglia
Authors: Black Joel A. , Liu Shujun , Waxman Stephen G. 
Published: December 2008

AbstractMicroglia provide surveillance in the central nervous system and become activated following tissue insult. Detailed mechanisms by which microglia detect and respond to their environment are not fully understood, but it is known that microglia express a number of surface receptors and ion channels, including voltage‐gated sodium channels, that participate in transduction of external stimuli to intra‐cellular responses. To determine whether activated microglia are affected by the activity of sodium channels, we examined the expression of sodium channel isoforms in cultured microglia and the action of sodium channel blockade on multiple functions of activated microglia. Rat microgliain vitroexpress tetrodotoxin (TTX)‐sensitive sodium channels Nav1.1 and Nav1.6 and the TTX‐resistant channel Nav1.5, but not detectable levels of Nav1.2, Nav1.3, Nav1.7, Nav1.8, and Nav1.9. Sodium channel blockade with phenytoin (40 μM) and TTX (0.3 μM) significantly reduced by 50–60% the phagocytic activity of microglia activated with lipopolysaccharide (LPS); blockade with 10 μM TTX did not further reduce phagocytic activity. Phenytoin attenuated by ∼50% the release of IL‐1α, IL‐1β, and TNF‐α from LPS‐stimulated microglia, but had minimal effects on the release of IL‐2, IL‐4, IL‐6, IL‐10, MCP‐1, and TGF‐α. TTX (0.3 μM) reduced, but to a smaller extent, the release of IL‐1α, IL‐1β, and TNF‐α from activated microglia. Phenytoin and TTX also significantly decreased by ∼50% adenosine triphosphate‐induced migration by microglia; studies with microglia cultured frommedmice (which lack Nav1.6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia. © 2008 Wiley‐Liss, Inc.
Secretory phospholipase A2plays an essential role in microglial inflammatory responses toMycobacterium tuberculosis
Authors: Yang Chul‐Su , Yuk Jae‐Min , Shin Dong‐Min , Kang Junghee , Lee Sung Joong , Jo Eun‐Kyeong 
Published: December 2008

AbstractIn previous studies, we have shown that reactive oxygen species (ROS)‐mediated inflammatory signaling is essential for microglial proinflammatory responses toMycobacterium tuberculosis(Mtb). To further investigate the molecular mechanisms governing these processes, we sought to describe the role of phospholipase A2(PLA2) in Mtb‐induced ROS generation and inflammatory mediator release by microglia. Inhibition of secretory PLA2(sPLA2), but not cytosolic PLA2(cPLA2), profoundly abrogated Mtb‐mediated ROS release, the generation of various inflammatory mediators (tumor necrosis factor, interleukin‐6, cyclooxygenase‐2, inducible nitric oxide synthase, and matrix metalloproteinase‐2 and −9), and the activation of nuclear factor (NF)‐κB and MAPKs (ERK1/2, p38, and JNK/SAPK) by murine microglial BV‐2 cells or primary mixed glial cells. Interruption of the Ras/Raf‐1/MEK1/ERK1/2 pathway abolished Mtb‐induced sPLA2activity, whereas the blockage of JNK/SAPK or p38 activity had no effect. Specific inhibition of sPLA2, but not cPLA2, suppressed the upregulation of ERK1/2 phosphorylation by Mtb stimulation, suggesting the existence of a mutual dependency between the ERK1/2 and sPLA2pathways. Moreover, examination of the protein kinase C (PKC) family revealed that classical PKCs are involved in Mtb‐induced sPLA2activation by microglia. Taken together, our results demonstrate for the first time that sPLA2, either through pathways comprising Ras/Raf‐1/MEK1/ERK1/2 or the classical PKC family, plays an essential role in Mtb‐mediated ROS generation and inflammatory mediator release by microglial cells. © 2008 Wiley‐Liss, Inc.
GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to glioblastoma in a Trp53 null background
Authors: Hede Sanna‐Maria , Hansson Inga , Afink Gijs B. , Eriksson Anna , Nazarenko Inga , Andrae Johanna , Genove Guillem , Westermark Bengt , Nistér Monica 
Published: December 2008

AbstractGlioblastomas are the most common and malignant astrocytic brain tumors in human adults. The tumor suppressor gene TP53 is commonly mutated and/or lost in astrocytic brain tumors and the TP53 alterations are often found in combination with excessive growth factor signaling via PDGF/PDGFRα. Here, we have generated transgenic mice over‐expressing human PDGFB in brain, under control of the human GFAP promoter. These mice showed no phenotype, but on a Trp53 null background a majority of them developed brain tumors. This occurred at 2–6 months of age and tumors displayed human glioblastoma‐like features with integrated development of Pdgfrα+ tumor cells and Pdgfrβ+/Nestin+ vasculature. The transgene was expressed in subependymal astrocytic cells, in glia limitans, and in astrocytes throughout the brain substance, and subsequently, microscopic tumor lesions were initiated equally in all these areas. With tumor size, there was an increase in Nestin positivity and variability in lineage markers. These results indicate an unexpected plasticity of all astrocytic cells in the adult brain, not only of SVZ cells. The results also indicate a contribution of widely distributed Pdgfrα+ precursor cells in the tumorigenic process. © 2008 Wiley‐Liss, Inc.
Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-β signaling from tumor suppression to oncogenesis in early chronic hepatitis B #
Authors: Murata Miki , Matsuzaki Koichi , Yoshida Katsunori , Sekimoto Go , Tahashi Yoshiya , Mori Shigeo , Uemura Yoshiko , Sakaida Noriko , Fujisawa Junichi , Seki Toshihito , Kobayashi Kazuki , Yokote Koutaro , Koike Kazuhiko , Okazaki Kazuichi 
Published: December 2008

Abstract
Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor β (TGF-β) signaling involves both tumor suppression and oncogenesis. TGF-β activates TGF-β type I receptor (TβRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TβRI-dependent pSmad3C transmitted a tumor-suppressive TGF-β signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TβRI/pSmad3C/p21WAF1 tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. Conclusion: HBx shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove clinically useful for predicting risk of HCC. (Hepatology 2009.)
Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats #
Authors: Chen Xiaocong , Sebastian Becky M. , Tang Hui , McMullen Megan M. , Axhemi Armend , Jacobsen Donald W. , Nagy Laura E. 
Published: December 2008

Abstract
Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular antioxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4 to 7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (CCAAT/enhancer binding protein α; peroxisome proliferator-activated receptor α/γ) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor α, normalizing adiponectin messenger (m)RNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated tumor necrosis factor α expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation. Conclusion: In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, tumor necrosis factor α expression, and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver tissue. (Hepatology 2009.)
Loss of protein kinase Cβ function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance #
Authors: Huang Wei , Bansode Rishipal , Mehta Madhu , Mehta Kamal D. 
Published: December 2008

Abstract
Obesity is an energy balance disorder in which intake is greater than expenditure, with most excess calories stored as triglyceride (TG). We previously reported that mice lacking the β-isoform of protein kinase C (PKCβ), a diacylglycerol- and phospholipid-dependent kinase, exhibit marked reduction in the whole body TG content, including white adipose tissue (WAT) mass. To investigate the role of this signaling kinase in metabolic adaptations to severe dietary stress, we studied the impact of a high-fat diet (HFD) on PKCβ expression and the effect of PKCβ deficiency on profound weight gain. We report herein that HFD selectively increased PKCβ expression in obesity-prone C57BL/6J mice, specifically in WAT; the expression levels were little or unchanged in the liver, muscle, kidney, and heart. Basal PKCβ expression was also found to be elevated in WAT of obese ob/ob mice. Remarkably, mice lacking PKCβ were resistant to HFD-induced obesity, showing significantly reduced WAT and slightly higher core body temperatures. Unlike lean lipodystrophic mouse models, these mice did not have fatty livers, nor did they exhibit insulin resistance. Moreover, PKCβ−/− mice exhibited changes in lipid metabolism gene expression, and such alterations were accompanied by significant changes in serum adipokines. These observations suggest that PKCβdeficiency induced a unique metabolic state congruous with obesity resistance, thus raising the possibility that dysregulation of PKCβ expression could contribute to dietary fat–induced obesity and related disorders. (Hepatology 2009.)
Supra‐normal age‐linked retrograde amnesia: Lessons from an older amnesic (H.M.)
Authors: MacKay Donald G. , Hadley Christopher 
Published: December 2008

AbstractMacKay and James (2001) demonstrated greater‐than‐normal retrograde amnesia (RA) for lexical‐semantic information in amnesic H.M., a deficit that worsened with aging or represented supranormal age‐linked RA (SARA). The present experiments extend these earlier observations to new types of information. Experiment 1 participants (H.M. and carefully matched memory‐normal controls) named pictures on the Boston Naming Test and H.M. correctly named reliably fewer pictures with low frequency names, he produced unusual naming errors, and he benefited reliably less than the controls from phonological cues to the target word. Experiment 2 participants recalled irregularly‐spelled aspects of familiar words in a two‐choice recognition memory task and H.M. chose the correct spelling reliably less often than the controls. Experiment 3 participants read low frequency words aloud at age 73 and H.M. produced reliably more reading errors than the controls. Results of all three experiments indicate supranormal RA (SRA) for information once familiar to H.M. and comparisons with earlier studies using similar or identical stimuli indicated that H.M.'s SRA has worsened with aging from 1980 to 1999. In short, H.M. exhibits SARA for phonological and orthographic information, consistent with the MacKay and James results and with interactions between aging and amnesia predicted under binding theory. © 2008 Wiley‐Liss, Inc.
Stimulation of NMDA and AMPA glutamate receptors elicits distinct concentration dynamics of nitric oxide in rat hippocampal slices
Authors: Frade J.G. , Barbosa R.M. , Laranjinha J. 
Published: December 2008

AbstractNitric oxide (•NO) is an intercellular messenger implicated in memory formation and neurodegeneration in the hippocampus. Owing to its physical and chemical properties, the concentration dynamics of•NO is a critical issue in determining its bioactivity as a signaling molecule. Its production is closely related to glutamateN‐methyl‐D‐aspartate (NMDA) receptors, following a rise in intracellular calcium levels. However, that dependent on α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors remains elusive and controversial, despite reports describing a role for these receptors in other brain regions, largely because of lack of quantitative and dynamic measurements of•NO. Using a•NO‐selective microsensor inserted in the diffusional spread of•NO in the CA1 region of rat hippocampal slices, we measured its real‐time endogenous production, following activation of ionotropic glutamate receptors and under tissue physiological oxygen tension. Both NMDA and AMPA stimulation resulted in a concentration‐dependent•NO production but encompassing distinct kinetics for lag phases and slower rates of•NO production were observed for AMPA stimulation. Robustness of the results was achieved instrumentally and pharmacologically, by means of nitric oxide synthase (NOS) inhibitors and antagonists of NMDA (D‐(−)‐2‐amino‐5‐phosphonopentanoic acid, AP5) and AMPA (2,3‐dioxo‐6‐nitro‐1,2,3,4‐tetrahydrobenzo[f]quinoxaline‐7‐sulfonamide, NBQX) receptors. When using glutamate as a stimulus,•NO production was of lower magnitude in the presence of AP5 plus NBQX than with AP5 alone, suggesting that even when NMDA receptors are inhibited Ca2+rises to levels to induce a peak of•NO from the background. Whereas extracellular Ca2+was required for the•NO signals, Philanthotoxin‐4,3,3 (PhTX‐4,3,3) a toxin used to target Ca2+‐permeable AMPA receptors, attenuated•NO production. These observations are interpreted on basis of a distinct coupling between the glutamate receptors and neuronal NOS. A role for Ca2+‐permeable AMPA receptors in the Ca2+activation of neuronal NOS is suggested. © 2008 Wiley‐Liss, Inc.
The effects of IL‐1 receptor antagonist on beta amyloid mediated depression of LTP in the rat CA1 in vivo
Authors: Schmid Adrien W. , Lynch Marina A. , Herron Caroline E. 
Published: December 2008

AbstractBeta‐amyloid (Aβ) is a neuro‐peptide implicated in the pathogenesis of Alzheimer's disease (AD). Aβ‐peptide is known to disrupt cellular processes, including synaptic plasticity. To date, the precise mechanisms leading to the Aβ‐mediated impairment of normal neurophysiological function still remains elusive. A rise in the pro‐inflammatory cytokine interleukin‐1‐β (IL‐1β) has been previously reported, following Aβ peptide insult. IL‐1β in turn, activates a cascade of pro‐apoptotic markers, gradually leading to cell death. In this work, we have investigated the possible protective effects of interleukin‐1 receptor antagonist (IL‐1ra) on the effects of Aβ‐peptide on long‐term potentiation (LTP) in the CA1 region of the rat hippocampus in vivo. We observed a significant depression of LTP in the group of animals that received intracerebroventricular (icv) injection of Aβ‐peptide (1–40) compared with control animals injected with vehicle. Administration of IL‐1ra alone (icv) also resulted in a depression of LTP; however, there was no change in the baseline synaptic response. Combined injection of Aβ(1–40) + IL‐1ra caused an attenuation of the effects observed with Aβ(1–40) alone for a period of up to 15 min following LTP induction; rescuing post‐tetanicpotentiation (PTP). Gradually however, EPSP‐values declined to produce a level of LTP similar to that observed following treatment with Aβ(1–40) alone. These results suggest that the acute Aβ‐mediated impairment of PTP and LTP may be partial as a result of activation of an inflammatory response and the release of IL‐1β. The attenuation of plasticity by IL‐1ra alone supports the theory that low levels of IL‐1β are required for normal synaptic plasticity. The limited rescue of the Aβ‐mediated effects on LTP, in the presence of IL‐1ra, may represent the short half life found with this receptor antagonist in vivo. © 2008 Wiley‐Liss, Inc.
Two‐dimensional physically based finite element runoff model for small agricultural watersheds: II. Model testing and field application
Authors: Bhardwaj Anil , Kaushal M. P. 
Published: December 2008

AbstractMathematical models are useful analysis tools to understand problems in watersheds associated with runoff, and to find solutions through land use changes and best management practices. However, before a model is applied in the field, it must be tested and checked to ensure that the model represents the real world adequately. In this paper, a two‐dimensional physically based finite element runoff model ROMO2D has been verified and validated by comparing the model output with analytic solution under simplified conditions, published data, and field measurements. Calibration of the model was done manually through a multi‐objective calibration procedure, using observed field data. Before going for field validation/application of ROMO2D, analysis was carried out to determine the optimum number of finite elements into which the watershed should be discretized and the size of the time step. A sensitivity analysis of the model was performed using the observed values of watershed parameters. The model was applied to a 1·45 ha agricultural watershed located in the Shiwalik foothills (India) to simulate runoff. The results demonstrated the potential of the model to simulate runoff from small agricultural watersheds for individual storm events with reasonable accuracy. Copyright © 2008 John Wiley & Sons, Ltd.