bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 1,25‐dihydroxyvitamin D3 by rat brain macrophages in vitro
Authors: Neveu I. , Naveilhan P. , Menaa C. , Wion D. , Brachet P. , Garabédian M. 
Published: January 2005

AbstractCultured microglial cells were examined for their ability to metabolize 25‐hydroxyvitamin D3 (25‐(OH) D3). Upon exposure to lipopolysaccharide, microglial cells produced a vitamin D metabolite which comigrated with synthetic 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3) in two different systems of high performance liquid chromatography. This metabolite had the same affinity as synthetic 1,25‐(OH)2D3 for the chick intestinal 1,25‐(OH)2D3 receptor. Lipopolysaccharide‐stimulated microglial cells incubated with 3 nM of 25‐(OH) D3 synthesized up to 5.76 fmol 1,25‐(OH)2D3/8 × 105 cells/2 hr. Microglial cells stimulated for 48 hr with interferon‐γ also produced a significant amount of 1,25‐(OH)2D3 (4.17 fmol/8 × 105 cells/2 hr). In contrast, levels of 1,25‐(OH)2D3 produced by resting microglial cells were barely detectable. It is concluded that activated brain macrophages may be committed to synthesize 1,25‐(OH)2D3 in vitro. This raises the possibility that activation of microglial cells in vivo may be followed by an increase in the level of 1,25‐(OH)2D3 in the central nervous system (CNS). These results support the emerging concept that the brain constitutes a target tissue for vitamin D metabolites. © 1994 Wiley‐Liss, Inc.
Molecular cloning and characterization of rat brain 2′, 3′ ‐cyclic nucleotide 3′ ‐phosphodiesterase isoform 2
Authors: Gravel M. , DeAngelis D. , Braun P. E. 
Published: January 2005

AbstractWe have isolated a cDNA coding for the larger isoform of the rat brain 2′,3′ ‐cyclic nucleotide 3′ ‐phosphodiesterase (CNP2), a protein associated with myelination in the central nervous system (CNS). The complete 420 amino acid sequence was deduced from the nucleotide sequence of the cDNA. Sequence comparisons show that rat CNP shares 96% homology with mouse, 84% with bovine, and 86% with human CNP. Errors in the published sequence of rat CNP1 have now been corrected. Comparisons with other proteins reveal several interesting conserved motifs, including two leucine repeat heptads, and two consensus motifs for phosphorylation in the N‐terminal domain of CNP2.© 1994 Wiley‐Liss, Inc.
Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist
Authors: Hindley S. , Herman M. A. R. , Rathbone M. P. 
Published: January 2005

AbstractAdenosine and its nucleotides adenosine triphosphate (ATP) and adenosine diphosphate (ADP) stimulate the proliferation of brain astrocytes in vitro and augment the effects of other growth factors. Following brain injury, hypoxia, or around solid tumors with necrotic centers, such as glioblastoma multiformes, high concentrations of adenine nucleotides and adenosine are released into the extracellular space; extracellular adenosine concentrations can rise 30–100‐fold to a concentration in excess of 100 μM. Increased concentrations of extracellular adenosine and adenine nucleotides may contribute to reactive astrocytic proliferation following brain injury. To test this hypothesis, adenosine, an adenosine analog 5′‐(N‐cyclopropyl)‐carboxamidoadenosine (CPCA), or ADP was microinjected into rat cortex. The number of glial fibrillary acidic prtein‐immunopositive cells was compared between the treated and contralateral saline‐injected hemispheres. Within 48 hr, astrocyte density around the CPCA (100 μM) infusion site was almost double that around the control saline infusion site. In hemispheres into which CPCA was infused, there was an increase in astrocytes in the subpial region along fiber tracts and around blood vessels, characteristic of Scherer's secondary structures found in association with malignant astrocytic brain tumors. The increased astrogliosis elicited by CPCA was abolished by coinfusion of the adenosine A2 receptor antagonist 1,3‐dipropyl‐7‐methylxanthine (DPMX). While microinjection of adenosine (1 mM) failed to stimulate astrogliosis, microinjection of ADP (500 μM) also resulted in a significant reactive astrogliosis and accumulation of astrocytes similar to Scherer's secondary structures. These data indicate that purine nucleosides and nucleotides may play a role in reactive astrogliosis following injury and may also play a role in stimulating the astrocyte migration responsible for Scherer's secondary structures around astrogliomas. © 1994 Wiley‐Liss, Inc.
Role for glial cells in regulating the functional expression of neuropeptide Y (NPY) neurons in aggregate cultures derived from dissociated fetal brain cells
Authors: Barnea A. , Cho G. , Lu G. 
Published: January 2005

AbstractA series of studies from our laboratory have established an aggregate culture system of fetal rat brain cells expressing neuropeptide Y (NPY) which can serve as a model to study the role of glia‐neuron paracrine interactions in the developmental expression of NPY neurons. In this system, NPY production increases progressively with culture‐age and it is induced by forskolin (FOR) and phorbol 12‐myristate 13‐acetate (PMA). We addressed the following question: Is the functional expression of the NPY neurons impaired in the absence of glial cells (particularly astrocytes) and if so, can secretory products of aggregates composed of the full complement of brain cells ( intact aggregates) restore the function of the impaired NPY neurons? Aggregates were generated from 17‐day‐old fetal rat cortex and maintained in serum‐free medium for 13–15 days. Cytosine arabinoside (CA; doses of 0.5–8 μM) was added to the cultures on day 1 and the effectiveness in elimination of glial cells was verified on day 15 by measuring the incorporation of 3H thymidine into DNA and by immunostaining for the astrocyte marker glial fibrillary acidic protein (GFAP). Basal NPY production and FOR (10 μM) + PMA (20 nM) stimulated production of NPY on days 13–15 were taken as functional criteria. FOR + PMA induced ≈2‐fold increase in NPY production in control cultures (no CA). CA inhibited both basal and FOR + PMA induced production of NPY and DNA synthesis in a dose‐dependent manner: at 6 μM CA, basal NPY production was reduced by about 50%, FOR + PMA stimulated production of NPY and DNA synthesis were completely inhibited, and astrocytes were essentially eliminated. A competing dose of 100 μM deoxycytidine completely reversed the effects of 6 μM CA on DNA synthesis and basal and FOR + PMA stimulated production of NPY. Conditioned media derived from intact aggregates completely restored basal and partially (≈50%) restored FOR + PMA stimulated production of NPY in CA‐treated aggregates. These results implicate secretory products of glial cells (astrocytes?) and/or glial‐neuron paracrine interactions in regulating the developmental expression of NPY neurons in culture such that activation of the cAMP and protein kinase C pathways leads to increased production of NPY. © 1994 Wiley‐Liss, Inc.
Four structurally distinct neuron‐specific olfactomedin‐related glycoproteins produced by differential promoter utilization and alternative mRNA splicing from a single gene
Authors: Danielson P. E. , Forss‐Petter S. , Battenberg E. L. F. , deLecea L. , Bloom F. E. , Sutcliffe J. G. 
Published: January 2005

AbstractFour structurally related neuron‐specific 1B426b mRNAs, designated AMY, BMY, AMZ, and BMZ, have been isolated from rat brain cDNA libraries. The four mRNAs are related to one another by their shared M region and by two pairs of alternative 5′ (A, B) or 3′ (Y, Z) regions. All four possible combinations were detected. The four transcripts are derived by differential promoter utilization (to generate A or B 5′ ends) and alternative splicing (to generate Y or Z 3′ ends) of the primary transcripts of the single D2Sutle gene. All four mRNAs were detected in most brain regions, but were enriched within the cortex and hippocampus. In the pituitary only the two A‐type and in the adrenal glands only the two B‐type mRNAs were detected. In situ hybridization shows a highly heterogeneous distribution across brain regions, paralleling the Northern blot results and additionally identifying the reactive cells as neurons. The cDNAs encode related glycoproteins of 125, 153, 457, and 485 amino acids, which have been detected immunochemically. The AMZ and BMZ proteins show significant sequence similarity with olfactomedin, an extracellular matrix protein of bullfrog olfactory epithelium, suggesting the possibility of a matrix‐related function for these rat glycoproteins in neurons and neurosecretory cells. © 1994 Wiley‐Liss, Inc.
Histamine‐mediated neuronal death in a rat model of Wernicke's encephalopathy
Authors: Langlais P. J. , Zhang S. X. , Weilersbacher G. , Hough L. B. , Barke K. E. 
Published: January 2005

AbstractThree experiments were conducted to examine the role of histamine in neuronal degeneration in a rat model of Wernick's encephalopathy induced by an acute bout of pyrithiamine‐induced thiamine deficiency (PTD). In the first experiment, histamine levels in medial thalamus of freely moving PTD rats measured by microdialysis were increased (180% of controls) at a prelesion stage of thiamine deficiency (treatment day 12) and further elevated 48 hr later (380%) in the same animals when necrosis was evident. Histamine levels in dialysates of the hippocampus collected simultaneously from the same animals were unchanged at either stage of thiamine deficiency. Glutamate levels in microdialysates from the same animals were unchanged at the prelesion stage but were significantly elevated on the second collection day. In a second experiment, separate groups of PTD and pairfed control (CT) rats were infused continuously with either α‐fluoromethylhistidine (FMH; 80 mg/day, i. p.), an irreversible inhibitor of histamine synthesis, or saline. FMH pretreatment produced a significant protection against PTD‐induced neuronal loss within the midline‐intralaminar and anteromedial thalamic nuclei, but had no effect on damage to ventrolateral nuclei, anteroventral nucleus, or the mammillary bodies. In a third study, histamine (80 μg, free base) or vehicle was directly infused into the same region of medial thalamus dialyzed in experiments 1. Histamine infusion into prelesion PTD but not CT animals resulted in severe neuronal loss and gliosis. Infusion of vehicle into the same regions of PTD and CT rats produced a mild gliosis restricted to the needle tract with no evidence of neuronal loss. These observations together with recent evidence of a histamine enhancement of glutamate receptor activation suggest that early histamine release may contribute significantly to glutamate‐N‐methyl‐D‐aspartate (NMDA)‐mediated excitotoxic neuronal death in thiamine deficiency‐induced Wernicke's encephalopathy. © 1994 Wiley‐Liss, Inc.
Oligodendroglial cyclic AMP response element‐binding protein: A member of the CREB family of transcription factors
Authors: Sato‐Bigbee C. , Chan E. L. P. , Yu R. K. 
Published: January 2005

AbstractSeveral laboratories have shown that cyclic AMP (cAMP) plays an important role in inducing oligodendrocyte differentiation and myelin synthesis. Our previous results have shown that oligodendrocytes contain a nuclear protein that binds to the DNA sequence TGACGTCA or cAMP response element (CRE) known to be involved in the transcriptional regulation of cAMP‐responsive genes. In this report the oligodendroglial CRE‐binding protein was further identified by using two different antibodies which specifically recognize the CRE‐binding protein known as CREB. In DNA‐shift assays CREB‐1 (X‐12) antibody interacted with the CRE‐protein complexes resulting in further retardation (“super shift”) of the mobility of the bands in the gels. Immunoprecipitation of oligodendroglial nuclear extracts with CREB(240) antibody prior to the DNA binding assays resulted in a lack of formation of CRE‐protein complexes. In addition immunoreaction with CREB(240) antibody identified the CRE‐binding species as a 45 kDa phosphoprotein. Immunocytochemical staining with CREB(240) antibody in oligodendrocytes from 10‐, 14‐, and 18‐day‐old and adult rats indicated that this protein in expressed before the appearance of myelin basic protein (MBP) which was used as a marker of myelin synthesis. Collectively, these observations support our previous results and indicate that the oligodendroglial CRE‐binding protein species is highly homologous to the CREB protein. The developmental expression of this CREB protein supports the idea of a possible role during the early stages of oligodendrocyte differentiation preceding the peak of myelin synthesis in rat CNS. © 1994 Wiley‐Liss, Inc.
Identification and characterization of batk, a predominantly brain‐specific non‐receptor protein tyrosine kinase related to Csk
Authors: Kuo S. S. , Moran P. , Gripp J. , Armanini M. , Phillips H. S. , Goddard A. , Caras I. W. 
Published: January 2005

AbstractA novel cDNA, brain‐associated tyrosine kinase (Batk), was isolated from a rat hippocampal library and appears to encode a new member of the Csk subfamily of non‐receptor protein tyrosine kinases, with 52% overall amino acid identity to rat Csk. Batk resembles kinases of the Src family in that it contains a Src homology 2 (SH2) domain and an SH3 domain, followed by a tyrosine kinase domain. Analysis of incompletely spliced Batk cDNAs suggests that the genomic structure of Batk is similar to that of Csk with identical exon/intron boundaries. Batk also shows significant homology (86% overall amino acid identity) to the recently described human megakaryocyte‐specific Matk. Although Batk is 41 amino acids shorter than Matk, Southern blot analysis suggests that Batk might be a rat homolog of Matk. Batk is predominantly expressed in the brain, with lower expression in the spleen and undetectable expression in other tissues. In situ hybridization and Northern blot analysis show that Batk is widely distributed throughout the adult brain, being primarily expressed in neurons, including those of the hippocampus and cortex. In contrast, embryos appear to have markedly decreased expression levels. Analysis of postnatal day 1 brain suggests that Batk may be upregulated at birth throughout the brain except in the cerebellum. In view of its homology to Csk, a negative regulator of Src family tyrosine kinases, and its generalized expression in the adult brain, we suggest that Batk may function as a brain‐specific regulator of kinases involved in the development and maintenance of the nervous system. © 1994 Wiley‐Liss, Inc.
Transcription of the brain creatine kinase gene in glial cells is modulated by cyclic AMP‐dependent protein kinase
Authors: Kuzhikandathil E. V. , Molloy George R. 
Published: January 2005

AbstractThe brain creatine kinase (CKB) gene is expressed in a variety of tissues with highest expression seen in the brain. We have previously shown in primary rat brain cell cultures that CKB mRNA levels are high in oligodendrocytes and astrocytes and low in neurons (Molloy et al.: J Neurochem 59:1925–1932, 1992). In this report we show that treatment of human U87 glioblastoma cells with forskolin and IBMX, to elevate intracellular cAMP, induces expression of CKB mRNA from the transiently transfected rat CKB gene by 14‐fold and also increases expression from the endogenous human CKB gene. This induction of CKB mRNA (i) is due to increased transcription; (ii) occurs rapidly (with maximal induction after 6 hr; iii) requires the activity of protein kinase A (PKA), but (iv) does not require de novo protein synthesis and, in fact, is superinduced in the presence of cycloheximide. Given the role of oligodendrocytes in the energy‐demanding process of myelination and of astrocytes in ion transport, these results have physiological significance, since they suggest that changes in cellular energy requirements in the brain during events, such as glial cell differentiation and increased neuronal activity, may in part be met by a cAMP‐mediated modulation of CKB gene expression. Of particular importance is the possible modulation of CKB gene expression during myelinogenesis, since oligodendrocyte differentiation has been shown previously to be stimulated by increases in cAMP. Copyright © 1994 Wiley‐Liss, Inc.
Myelin basic protein mediates extracellular signals that regulate microtubule stability in oligodendrocyte membrane sheets
Authors: Dyer C. A. , Philibotte T. M. , Wolf M. K. , Billings‐Gagliardi S. 
Published: January 2005

AbstractTreatment of cultured oligodendrocytes with a monoclonal antibody to galactocerebroside (GalC) triggers a cascade of events including the redistribution of membrane surface GalC over internal domains of MBP and loss of microtubular structures within the sheets (Dyer and Benjamins: J Neurosci 8:4307–4318, 1988; Dyer and Benjamins: J Neurosci Res 24:212–221, 1989). In this report, wild type and myelin basic protein (MBP)‐deficient shiverer oligodendrocytes were used to study the possible relationships between these events, and specifically to determine if MBP mediates signals which destabilize microtubular assemblies in cultured oligodendrocytes. We now show that MBP and GalC, which are both initially Triton X‐100 soluble, become Triton X‐100 insoluble following anti‐GalC binding and anti‐GalC:GalC complex redistribution, suggesting that the surface anti‐GalC: GalC complexes become associated with cytoplasmic MBP. Mediation of the signaling event by MBP is further demonstrated by (1) a decreased phosphorylation of MBP in wild type oligodendrocytes after antibody binding, and (2) the absence of responses, such as GalC redistribution and microtubule loss, in MBP‐deficient shiverer oligodendrocytes treated with anti‐GalC. Continuous activation of the GalC/MBP pathway for 7 days in wild type oligodendrocytes results in enlarged cell bodies and production of numerous microprocesses, a morphology that is similar to MBP‐deficient shiverer oligodendrocytes. A second signaling pathway which produces an opposite effect, i.e., the stabilization and apparent up‐regulation of microtubular structures in cultured oligodendrocyte membrane sheets, remains functional in shiverer oligodendrocytes. Thus, MBP appears to be important for mediating extracellular signals that cause a loss of microtubular structures in oligodendrocyte membrane sheets and abnormal morphology. Copyright © 1994 Wiley‐Liss, Inc.
The insulin‐like growth factor I system in the rat cerebellum: Developmental regulation and role in neuronal survival and differentiation
Authors: Torres‐Aleman I. , Pons S. , Arévalo M. A. 
Published: January 2005

AbstractThe developmental regulation of insulin‐like growth factor I (IGF‐I), its receptor, and its binding proteins (IGFBPs) was studied in the rat cerebellum. All the components of the IGF‐I system were detectable in the cerebellum at least by embryonic day 19. Levels of IGF‐I receptor and its mRNA were highest at perinatal ages and steadily decrease thereafter, although a partial recovery in IGF‐I receptor mRNA was found in adults. Levels of IGF‐I and its mRNA also peaked at early ages, although immunoreactive IGF‐I showed a second peak during adulthood. Finally, levels of IGFBPs were also highest at early postnatal ages and abruptly decreased thereafter to reach lower adult levels. Since highest levels of the different components of the IGF‐I system were found at periods of active cellular growth and differentiation we also examined possible trophic effects of IGF‐I on developing cerebellar cells in vitro. We found a dose‐dependent effect of IGF‐I on neuron survival together with a specific increase of the two main neurotransmitters used by cerebellar neurons, GABA and glutamate. Analysis of cerebellar cultures by combined in vitro autoradiography and immunocytochemistry with cell‐specific markers indicated that both Purkinje cells (calbindin‐positive) and other neurons (neurofilament‐positive) contain IGF‐I binding sites. These results extend previous observations on a developmental regulation of the IGF‐I system in the cerebellum and reinforce the notion of a physiologically relevant trophic role of IGF‐I in cerebellar development. © 1994 Wiley‐Liss, Inc.
Axonal transport of type III intermediate filament protein peripherin in intact and regenerating motor axons of the rat sciatic nerve
Authors: Chandan S. , Le Gall J.‐Y. , di Giamberardino L. , Filliatreau G. 
Published: January 2005

AbstractSlow axonal transport of peripherin has been studied in the motor axons of both intact and regenerating rat sciatic nerves 7 days post‐crush. The studies were done by two‐dimensional gel electrophoresis after intraspinal injection of35S‐methionine.In the first experiment, the sciatic nerves were removed 3 weeks after the radiolabeling pulse and cut into 6 mm segments. Each nerve segment was submitted to two‐dimensional gel electrophoresis and analyzed by an original procedure which allowed us to study the distribution along the nerve of the radioactivity associated with several proteins of the cytoskeleton, especially the intermediate filament proteins, peripherin, and the low molecular mass neurofilament protein, NF‐L. Peripherin was transported at two main rates: 66% of the total radiolabeled peripherin moved at 1.42 mm/day and the remainder moved at 2.28 mm/day. The radioactivity associated with NF‐L exhibited a similar pattern.In the second experiment, similar intraspinal injections were made 7 days after a unilateral crush of the sciatic nerve. Regenerating nerves exhibited a clear SCa wave. However, in contrast to the intact nerves, the SCb wave could not be precisely defined in the regenerating nerves. Thus, the changes in the amount of transported proteins were analyzed in the SCa wave only. Autoradiograms of 2D‐PAGE revealed that in the regenerating axons, the quantity of transported peripherin in SCa was increased by 3.5‐fold. In contrast, the quantity of transported NF‐L was decreased by 1.6‐fold. The regenerating motor axons conveyed significantly greater (approximately twofold) amounts of labeled tubulins and actin than did intact motor axons.Our results suggest that peripherin, although mainly conveyed by SCa, plays a role during the elongation process in addition to actin and tubulin. © 1994 Wiley‐Liss, Inc.
Long‐lasting accumulation of hemopexin in permanently transected peripheral nerves and its down‐regulation during regeneration
Authors: Madore N. , Sagot Y. , Guinaudy M. J. , Cochard P. , Swerts J. P. 
Published: January 2005

AbstractWe have previously demonstrated that hemopexin is present in the intact sciatic nerve and is overproduced in the distal stump after nerve transection (Swerts et al.: J Biol Chem 267:10596–10600, 1992). To get further insight into the function of this hemoprotein in nervous tissue, we have documented long‐term changes in hemopexin levels in permanently degenerated (transected) and regenerting (crush‐lesioned) sciatic nerves of adult rats, using immunochemical techniques. As early as a couple of days after nerve transection, the amount of hemopexin was raised in the distal stump and at the end of the proximal stump. Similarly, after a crush lesion hemopexin was rapidly increased at the injury site and in the distal part of the nerve. Subsequently, in transected nerves the level of hemopexin rose steadily and remained elevated, representing, three months after injury, over 20 times the amount found in intact contralateral nerves. In contrast, in crush‐lesioned nerves, hemopexin level declined progressively in a proximodistal direction and returned to basal values 2 months after injury, together with axonal regeneration. This long‐term increase in hemopexin in permanently degenerated nerves and its progressive return to normal levels during nerve regeneration suggests that hemopexin content could be regulated negatively, directly or indirectly, by growing axons. In turn, these results support the idea that hemopexin could be involved in the process of Wallerian degeneration and/or in nerve repair. © 1994 Wiley‐Liss, Inc.