bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of choline acetyl transferase activity by l‐ and d‐carnitine in brain areas of neonate rats
Authors: Ayala C. A. 
Published: January 2005

AbstractAcetyl‐CoA supply to the cytosol and its regulatory influence on acetylcholine biosynthesis is still an unsolved question. Acetylcarnitine through the carnitine acetyl transferase (CarAT) system has been proposed to be the acetyl donor in this process. Carnitine isomers were injected into rat developing brains every day for 14 days after birth. Results showed that carnitine and its associated forms produced a choline acetyl transferase (ChAT) activity increase in the striatum and the hippocampus. Carnitine acetyl transferase activity was stimulated by the treatment of 1‐carnitine in the hippocampus but it remained unchanged in the striatum and the cerebral cortex. These results suggest that ChAT and CarAT activities might be modulated by Acetyl‐CoA derived preferentially from acetylcarnitine. It is suggested that ChAT activity enhancement depends on intrinsic and extrinsic cholinergic afferents to these brain areas. © 1995 Wiley‐Liss, Inc.
Thyroid hormone and conditioned medium effects on astroglial cells from hypothyroid and normal rat brain: Factor secretion, cell differentiation, and proliferation
Authors: Trentin A. G. , Rosenthal D. , Neto V. Moura 
Published: January 2005

AbstractThe effects of triiodothyronine (T3)on cell morphology were examined in cerebral hemisphere and cerebellar astrocyte cultures obtained from normal and hypothyroid neonatal rats. T3‐treatment induced morphological changes in astrocytes from cerebral hemispheres. This morphological effect was produced earlier if astrocytes were treated with conditioned medium obtained from cerebral hemisphere astrocyte cultures previously exposed to 50 nM T3. T3 or conditioned medium‐treatment produced faster morphological changes in hypothyroid rat cerebral hemisphere astrocyte monolayers. Cerebellar astrocytes from normal brain did not respond to thyroid hormone with morphological changes, but proliferated after T3‐treatment. However, hypothyroid cerebellar astrocyte cultures exhibited morphological changes, differently than normal cells.We verified that T3 may induce astrocyte secretion of factor(s) that promotes morphological differentiation in cerebral hemisphere astroglial cultures and stimulates the proliferation of cerebellar astrocytes. Astrocytes obtained from hypothyroid animals were more sensitive to secreted factors than normal cells. These results emphasize the heterogeneity and the importance of glial cells to normal brain development and open new questions about thyroid hormone therapy in hypothyroidism. © 1995 Wiley‐Liss, Inc.
Expression of the nerve growth factor gene is controlled by the microtubule network
Authors: Baudet C. , Naveilhan P. , Jehan F. , Brachet P. , Wion D. 
Published: January 2005

AbstractColchicine, nocodazol, and vinblastine, three microtubule‐disrupting drugs were shown to increase the levels of both nerve growth factor (NGF) mRNA and cell‐secreted NGF protein in L929 cells, with levels of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) or amyloid precursor protein (APP) mRNAs remaining unaffected. Northern blot analysis demonstrated that colchicine also increased NGF mRNA levels in rat primary astrocytes and mouse skin fibroblasts. The specificity of the effects observed was assessed by the fact that the microtubulestabilizing agent Taxotere®, a semisynthetic compound structurally related to taxol, suppressed the effects of colchicine, whereas lumicolchicine, a colchicine derivative that has no action on the microtubule network, had no influence on NGF expression. Likewise, the disruption of the microfilament network by cytochalasin B did not increase NGF mRNA levels in L929 cells. Furthermore, the increase in NGF gene expression observed following microtubule disruption depended on a cascade of events involving at least one protein kinase, which is not down‐regulated by phorbol ester, and on a pertussis toxin sensitive step. These results support the concept that tubulin and/or the microtubule cytoskeleton play an active role in the regulation of the NGF gene. © 1995 Wiley‐Liss, Inc.
Deciphering the native GABAA receptor: Is there hope?
Authors: Yeh H. H. , Grigorenko E. V. 
Published: January 2005

AbstractThe bewildering number of GABAA receptor subunits, their regionally dependent expression in the brain, and their supernumerary expression in single cells present major challenges in studying the function of native GABAA receptors. Which subunit combinations actually exist in native neurons? In this mini‐review, GABAA receptor subunit diversity is considered in light of using the wealth of “structure‐function” information gained from studying recombinant receptor to predict the subunit composition and functional properties of native GABAA receptors. © 1995 Wiley‐Liss, Inc.
Increase in GAP‐43 and GFAP immunoreactivity int the rat hippocampus subsequent to perforant path kindling
Authors: Dalby N. O. , Rondouin G. , Lerner‐Natoli M. 
Published: January 2005

AbstractKindling is an animal model of epilepsy which is accompanied by morphological and biochemical changes in the brain, including sprouting of fibers and increased transmitter release. Here we have examined the immunocytochemical expression of (1) GAP‐43, a growth‐associated protein, which is a neuron‐specific PKC substrate, particularly expressed in development and regeneration and (2) glial fibrillary acidic protein (GFAP), part of the astrocytic cytoskeleton, after perforant path kiraling. Subsequent to kindling, GAP‐43 imimunoreacliviiy was increased in CAI stratum lacunosum‐moleculare and the inner and outer molecular layer of the fascia dentata. Other hippocampal subregions showed a lower increase. GFAP immunoreactivity was increased in the entire hippocampus, but especially in stratum lacunosum‐moleculare of the CAI and the hilus of fascia dentata. The difference between the number of GFAP‐positive profiles in the hippocampus of control rats and in fully kindled rats was found to be non‐significant. We interpret these findings as being related to both plastic neuronal changes and possible neuronal degeneration. © 1995 Wiley‐Liss, Inc.
Specificity of nerve growth factor signaling: Differential patterns of early tyrosine phosphorylation events induced by NGF, EGF, and bFGF
Authors: Blumberg D. , Radeke M. J. , Feinstein S. C. 
Published: January 2005

AbstractThe specificity of nerve growth factor (NGF) action was examined by comparing early tyrosine phosphorylation events induced by NGF, epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF). In PC12 cells, administration of either the differentiation factor NGF or the mitogenic factor EGF led to tyrosine phosphorylation of multiple polypeptides in the 100–110 kDa size range associated with PI‐3 kinase. However, NGF induced a more prolonged phosphorylation, relative to a transient EGF effect. In contrast, the differentiation factor bFGF failed to induce measurable tyrosine phosphorylation of PI‐3 kinase‐associated proteins. Similarly, NGF but not bFGF induced marked tyrosine phosphorylation of PLCγ, another early signaling molecule, suggesting that multiple pathways exist for promoting differentiation, and/or that these signaling molecules are not essential for differentiation. TrkA signaling was also compared between PC 12 cells and NIH‐3T3 cells heterologously expressing trkA, where receptor activation promotes mitogenesis. In this comparison, significant differences were observed in the tyrosine phosphorylation pattern of PI‐3 kinase‐associated polypeptides, suggesting the existence of cell type‐specific molecular interactions influencing trkA signaling. Mechanistically, NGF stimulation of PC12 cells resulted in a weak or possibly indirect association between trkA and PI‐3 kinase. Furthermore, NGF did not appear to activate or substantially alter the overall level of PI‐3 kinase activity, raising the possibility that ligand‐induced phosphorylation may serve instead to relocalize constitutively active PI‐3 kinase molecules within the cell. Taken together, data presented suggest that the temporal pattern of induced phosphorylation, the nature of induced associations with other phosphoproteins, and cell type‐specific components may all contribute to the generation of NGF signaling specificity. © 1995 Wiley‐Liss, Inc.
Differentiation is induced in three‐dimensional cultures of brain cells immortalized by the LAP mammalian regulatory system
Authors: Toth M. , Shenk T. , Madarasz E. 
Published: January 2005

AbstractImmortalized neuroectodermal precursor cell lines were generated from mouse brain by the SV40 large T antigen expressed under the control of the LAP (lac activating protein) mammalian regulatory system. The LAP system permits the reversible expression of T antigen as a function of the exogenous inducer, isopropyl‐β‐D‐thiogalactopyranoside. Immortalized cells can be stably maintained in an undifferentiated state in monolayer cultures. Cell lines expressed the early neurofilament‐like protein nestin, but not markers characteristic for mature cells such as the neurofilament light protein and glial fibrillary acidic protein. Downregulating the LAP‐controlled T antigen with isopropyl‐β‐D‐thiogalactopyranoside was not sufficient to induce differentiation. However, when cells formed three‐dimensional aggregates, differentiation to a neuronal phenotype occurred, indicating that cell‐cell interaction plays an important role in their differentiation. Cells in aggregates did not proliferate, even in the presence of T antigen, suggesting that an aggregation‐induced signal to cease growth was dominant over the growth signal of T antigen. Further morphological differentiation was induced by basic fibroblast growth factor. These immortalized cells should facilitate molecular and cellular studies concerned with the mechanism of commitment, fate determination, and mitotic arrest of neuronal precursor cells in the developing mammalian CNS. © 1995 Wiley‐Liss, Inc.
Differential expression of heat shock protein HSP27 in human neurons and glial cells in culture
Authors: Satoh J.‐I. , Kim S. U. 
Published: January 2005

AbstractHSP27 expression was investigated in cultured neurons and glial cells isolated from fetal human brains using immunoblotting and immunocytochemistry. Under unstressed conditions, HSP27 was identified at a high level in astrocytes (>99%), at a low level in neurons (7%), and at a minimally detectable level in microglia (<1%), whereas it was undetectable in oligodendrocytes. Under these conditions, HSP27 was located in the cytoplasm, fractionated into the Triton X‐100‐soluble phase, and composed chiefly of the basic isoform (HSP27a). After exposure to heat stress (43°C90 min), the level of HSP27 exproion ryas not altered in astrocytes but was elevated significantly in neurons (11–21%) and microglia (4–7%) during 8–48 hr postrecovery periods, while it remained undetectable in oligodendrocytes. In addition, various human neural cell lines exhibited differential patterns of HSP27 expression under unstressed and heat‐stressed conditions. Following heat shock treatment (45°C/30 min), granular aggregates of HSP27 were identified in the cytoplasm of astrocytes. Under heat‐stressed conditions, HSP27 was distributed within the Triton X‐100‐insoluble fraction associated with an increase in two more acidic isoforms (HSP27b and HSP27c). HSP27 and αβ‐crystallin were coexpressed in astrocytes under unstressed and heat‐stressed conditions. When astrocytes were exposed to known HSP27 inducers, hydrogen peroxide and cysteamine reduced the synthesis of HSP27, while estradiol showed no effects. The differential patterns of constitutive and heat‐induced expression of HSP27 in cultured human neurons and glial cells suggest that the cellular mechanisms by which HSP27 expression is regulated are different among various cell types in the human central nervous system. © 1995 Wiley‐Liss, Inc.
Distribution of erb‐b2, erb‐b3, and erb‐b4 in the developing avian nervous system
Authors: Francoeur J. R. , Richardson P. M. , Dunn R. J. , Carbonetto S. 
Published: January 2005

AbstractThe neuregulin proteins (GGF/ARIA/NDF/Heregulin) are pleiotrophic growth and differentiation factors whose receptors, erb‐B2, erb‐B3, and erb‐B4, are members of the epidermal growth factor receptor family of receptor tyrosine kinases. With western blots, we have examined the developmental and regional distribution of these receptors within the brain and sciatic nerve of chick embryos. The receptors erb‐B2, erb‐B3, and erb‐B4 are development and spatially regulated within the nervous system. In addition, cultures enriched for neurons or glia indicate that erb‐B2 and erb‐B4 are found in both neurons and glia, whereas erb‐B3 is found in glia alone. © 1995 Wiley‐Liss, Inc.
Excitatory amino acid receptors in glia: Different subtypes for distinct functions?
Authors: Gallo V. , Russell J. T. 
Published: January 2005

AbstractIt is now well established that expression of voltage‐ and ligand‐gated ionic channels, as well as G proteincoupled receptors, is not a property unique to neurons, but is also shared by macroglial cells (astrocytes and oligodendrocytes). These glial cells can receive a variety of signals from neurons at different stages of their development. Activation of membrane receptors may affect glial cell activity, proliferation, maturation, and survival through a complex cascade of intracellular events leading to long‐term changes in glial cell phenotype and functional organization. Here we review the experimental evidence for glutamate receptor expression in glial cells in culture and in situ, and the molecular and functional properties of these receptors. We also describe some experimental models that identify possible functions of glutamate receptors in glia. Now that the existence of glutamate receptors in glia has been unambiguously demonstrated, future research will have to (1) determine which receptor subtypes are expressed in macroglial cells in vivo; (2) analyze, in adequate experimental models, the short and long‐term changes produced by glutamate receptor activation in glia; and (3) establish whether these receptors play a role in neuron‐glia communication in the brain. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Several extracellular domains of the neural cell adhesion molecule L1 are involved in homophilic interactions
Authors: Holm J. , Appel F. , Schachner M. 
Published: January 2005

AbstractThe neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. It can interact with itself by a self‐binding, i.e., homophilic adhesion mechanism (Kadmon et al.: J Cell Biol 110: 193‐208, 1990a). To determine the domains of L1 involved in homophilic binding, we have generated protein fragments of Ll in a prokaryotic and a eukaryotic expression system and used these covalently coupled to fluorescent microspheres to quantify aggregation between them by cytofluorometric analysis. Protein fragments containing the first and second Ig‐like domains and the third fibronectin type III homologous repeat showed avid self‐binding. Ig‐like domains III and IV also showed some self‐binding, whereas Ig‐like domains V and VI and fibronectin type III homologous repeats 1 and 2 as well as 4 and 5 were less or not active. Binding between different domains was also observed: fibronectin type III homologous repeats 4 and 5 interacted with Ig‐like domains I and II, and fibronectin type III homologous repeats 3‐5 interacted with all Ig‐like domains. These results were confirmed by experiments testing the binding of fragment‐conjugated microspheres to substrate‐coated L1 or to cell surface‐expressed L1 on cultured neurons. Binding of L1 to itself was interfered with by all protein fragments tested, suggesting that also less avidly binding domains of L1 contribute to homophilic binding. These observations indicate prominent functional roles of both Ig‐like domains and fibronectin type III homologous repeats in homophilic binding of L1. © 1995 Wiley‐Liss, Inc.
Expression of neurotrophins in skeletal muscle: Quantitative comparison and significance for motoneuron survival and maintenance of function
Authors: Griesbeck O. , Parsadanian A. Sh. , Sendtner M. , Thoenen H. 
Published: January 2005

AbstractNeurotrophins play a crucial role in the regulation of survival and maintenance of specific functions of various populations of neurons. Brain‐derived neurotrophic factor (BDNF), newrotrophin‐3 (NT‐3) and neurotrophin 4/5 (NT‐4) have been shown to support motoneuron survival during embryonic development and, after birth, to protect motoneurons from degeneration after nerve lesion. We have compared the levels of these neurotrophins in skeletal muscle by quantitative Northern blot analysis, both during embryonic development and postnatally. We localized the sites of expression of these neurotrophins by in situ hybridisation and analysed the expression of trkB in the spinal cord by in situ hybridisation and immunohistochemistry. NT‐3 is most abundantly expressed both during embryonic development and in the postnatal phase, followed by NT‐4. The levels of BDNF are very low, in particular after birth. After nerve lesion, NT‐3 mRNA essentially remained unchanged, whereas NT‐4 mRNA rapidly decreased. The slow increase in BDNF expression seems to be essentially due to the expression in Schwann cells rather than skeletal muscle, demonstrated by in situ hybridisation. Our data indicate that motoneurons can receive trophic support from several members of the neurotrophin gene family during the period of naturally occurring cell death. Postnatally, the predominant ligand acting via trkB on motoneurons is NT‐4, whereas BDNF expression seems to play a role mainly after nerve lesion. © 1995 Wiley‐Liss, Inc.
Increased cyclic AMP in in vitro regenerating frog sciatic nerves inhibits Schwann cell proliferation bur has no effect on axonal outgrowth
Authors: Ekström P. A. R. 
Published: January 2005

AbstractIn the present study the role of cAMP for axonal outgrowth and Schwann cell proliferation was studying using the cultured frog sciatic nerve. An intrinsic rise in nerve injury, both in vitro and in vivo. Treatment with 0.1‐1.0μM forskolin, an activator of the cAMP‐generating enzyme adenylyl cyclase, increased the cAMP content up to 13‐fold, but was yet without effect on axonal outgrowth during an 8‐day culturing period. HA‐1004, an inhibitor of cAMP‐dependent protein kinase, also lacked effect on the regeneraton. In contrast, the proliferation of Schwann cells, measured as [3H]thymidine incorporation, was inhibited to about 70% of control by forskolin, whereas HA‐1004 stimulated proliferation to approximately 130% of control. The results suggest that cAMP is involved in the injury‐induced proliferation of Schwann cells of an adult peripheral nerve but that it lacks a central role in the regeneration of sensory axons of such nerves. © 1995 Wiley‐Liss, Inc.
Association of nerve growth factor mRNA levels with MK‐801‐induced explosive behaviors in mice
Authors: Riley L. A. , Hitri A. , Bernstein J. J. 
Published: January 2005

AbstractMK‐801, a noncompetitive antagonist of the N‐methyl‐D‐aspartate (NMDA) receptor, stimulated an outbred strain of NIH Swiss mice to display discrete episodes of explosive jumping behavior, designated as “popping.” The rapid onset of the MK‐801‐induced “popping” seems to follow the rapid distribution of the drug to the frontal cortex, the area that contains high levels of NMDA receptors. We examined the effect of this drug on the levels of mRNA coding for nerve growth factor (NGF) in the frontal cortex in relation to the exhibited “popping” episodes. Mice treated with 1 mg/kg MK‐801 could be split into two groups based on the total number of “popping” episodes in a 30 min post‐injection period. These groups also differed in the steady‐state levels of frontal cortex NGF mRNA. Animals that exhibited low numbers of “popping” had levels of NGF mRNA significantly higher than saline treated controls or mice that exhibited high numbers of “popping.” Mice treated with 10 mg/kg MK‐801 had a high frequency of “popping” that was impossible to separate into episodes. In addition, these mice had levels of frontal cortex NGF mRNA that were significantly lower than either group of mice treated with 1 mg/kg MK‐801. These data indicated that there was an increased level of NGF mRNA under conditions where MK‐801 induced a low level of “popping” behavior. However, when “popping” intensified, NGF mRNA levels were decreased, suggesting a possible behavioral antagonism of the NGF response. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Differentiation of serum‐free mouse embryo cells into astrocytes is accompanied by induction of glutamine synthetase activity
Authors: Loo D. T. , Althoen M. C. , Cotman C. W. 
Published: January 2005

AbstractSerum‐free mouse embryo (SFME) cells derived in a defined serum‐free medium have been cultured for more than 200 generations and display properties of neural progenitor cells. SFME cells express the neuroepithelial stem cell marker nestin in defined serumfree medium. Exposure of SFME cells to transforming growth factor beta (TGF‐β) or serum decreases nestin expression and induces the astrocyte marker glial fibrillary acidic protein, suggesting that SFME cells differentiate into astrocytes upon exposure to TGF‐β or serum. We examined the expression by SFME cells of the functional central nervous system (CNS) astrocyte marker glutamine synthetase (GS). GS activity is induced in SFME cells upon exposure to TGF‐β or serum. The induction of GS activity was dose‐ and time‐dependent and was reversible. Retinoic acid, hydrocortisone, and dibutyryl cyclic AMP also induced GS expression. The induction of GS activity was accompanied by an increase in the level of GS mRNA and protein. This work provides further evidence that SFME cells represent neural progenitor cells which differentiate into functional astrocytes upon exposure to TGF‐β or serum. © 1995 Wiley‐Liss, Inc.
Calpain secreted by activated human lymphoid cells degrades myelin
Authors: Deshpande R. V. , Goust J. M. , Hogan E. L. , Banik N. L. 
Published: January 2005

AbstractCalpain secreted by lymphoid (MOLT‐3, M.R.) or monocytic (U‐937, THP‐1) cell lines activated with PMA and A23187 degraded myelin antigens. The degradative effect of enzymes released in the extracellular medium was tested on purified myelin basic protein and rat central nervous system myelin in vitro. The extent of protein degradation was determined by SDS‐PAGE and densitometric analysis. Various proteinase inhibitors were used to determine to what extent protein degradation was mediated by calpain and/or other enzymes. Lysosomal and serine proteinase inhibitors inhibited 20‐40% of the myelindegradative activity found in the incubation media of cell lines, whereas the calcium chelator (EGTA), the calpain‐specific inhibitor (calpastatin), and a monoclonal antibody to m calpain blocked myelin degradation by 60‐80%. Since breakdown products of MBP generated by calpain may include fragments with antigenic epitopes, this enzyme may play an important role in the initiation of immune‐mediated demyelination. © 1995 Wiley‐Liss, Inc.