bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuritogenic and survival‐promoting effects of the P2 peptide derived from a homophilic binding site in the neural cell adhesion molecule
Authors: Pedersen Martin V. , Køhler Lene B. , Ditlevsen Dorte K. , Li Shizong , Berezin Vladimir , Bock Elisabeth 
Published: December 2003

AbstractThe neural cell adhesion molecule (NCAM) plays a pivotal role in neural development, regeneration, and plasticity. NCAM mediates adhesion and subsequent signal transduction through NCAM–NCAM binding. Recently, a peptide ligand termed P2 corresponding to a 12‐amino‐acid sequence in the FG loop of the second Ig domain of NCAM was shown to mimic NCAM homophilic binding as reflected by induction of neurite outgrowth in hippocampal neurons. We demonstrate here that in concentrations between 0.1 and 10 μM, P2 also induced neuritogenesis in primary dopaminergic and cerebellar neurons. Furthermore, it enhanced the survival rate of cerebellar neurons although not of mesencephalic dopaminergic neurons. Moreover, our data indicate that the protective effect of P2 in cerebellar neurons was due to an inhibition of the apoptotic process, in that caspase‐3 activity and the level of DNA fragmentation were lowered by P2. Finally, treatment of neurons with P2 resulted in phosphorylation of the ser/thr kinase Akt. Thus, a small peptide mimicking homophilic NCAM interaction is capable of inducing differentiation as reflected by neurite outgrowth in several neuronal cell types and inhibiting apoptosis in cerebellar granule neurons. © 2003 Wiley‐Liss, Inc.
Regulation of sphingomyelinases in cells of the oligodendrocyte lineage
Authors: Testai F.D. , Landek M.A. , Dawson G. 
Published: December 2003

AbstractControversy exists regarding the nature of the “executioner” sphingomyelinase (SMase) in cells and its subcellular localization. A new fluorescence‐based assay with the substrate 6‐hexadecanoylamino‐4‐methylumbelliferyl‐phosphorylcholine allowed rapid and reliable microassays of neutral (N) and acid (A) SMase activity in cell extracts from primary cultures of neonatal rat oligodendrocytes (OPC) and a human oligodendroglioma cell line (HOG). Total SMase activity was much higher in OPC than in HOG cells. Both staurosporine and tumor necrosis factor‐α (TNF‐α) induced apoptosis and activated NSMase in a multiphasic manner in both OPC and HOG cells. The increase in caspase 8 activity preceded the 1 hr peak of NSMase activation, which was followed by caspase 3 activation. In contrast, ASMase activity, which constituted >90% of the total SMase activity, was unresponsive to proapoptotic drugs. Neither reducing ASMase levels by 50% by pretreatment with desipramine nor inhibiting sphingolipid synthesis by 50% with fumonisin B1 had any effect on cell death. Isolation of sphingolipid‐rich plasma membrane microdomains (rafts) from the cells by sucrose density gradient ultracentrifugation revealed an enrichment of sphingomyelin, ceramide, and caspase 8. Proapoptotic drugs such as staurosporine promoted the translocation of NSMase to the raft fraction. In contrast, ASMase, other lysosomal hydrolases, and caspase 3 remained absent from rafts even after staurosporine treatment. The staurosporine‐induced concomitant increase of ceramide in the raft fraction and caspase 3 in the cytosol could be mimicked by the addition of exogenous bacterial SMase. We conclude that caspase 8 activates NSMase in rafts in oligodendrocytes and that the downstream apoptotic signal is via caspase 3. © 2003 Wiley‐Liss, Inc.
Astrocytes in culture require docosahexaenoic acid to restore the n‐3/n‐6 polyunsaturated fatty acid balance in their membrane phospholipids
Authors: Champeil‐Potokar Gaëlle , Denis Isabelle , Goustard‐Langelier Bénédicte , Alessandri Jean‐Marc , Guesnet Philippe , Lavialle Monique 
Published: December 2003

AbstractDocosahexaenoic acid (DHA), the main n‐3 polyunsaturated fatty acid (PUFA) in membranes, is particularly abundant in brain cells. Decreased cerebral concentrations of DHA, resulting from dietary n‐3 deficiency, are associated with impaired cognitive function. Because the cellular causes of this impairment are still unknown, we need in vitro models that mimic the variations in n‐3/n‐6 PUFA seen in vivo. We have compared the PUFA profiles of hamster astrocytes cultured in medium supplemented with long‐chain PUFA [DHA and/or arachidonic acid (AA)] with those of brain tissue from hamsters fed an n‐6/n‐3 PUFA‐balanced diet or one lacking n‐3 PUFA. Astrocytes were obtained from the brain cortex of newborn hamsters and cultured in minimum essential medium + 5% fetal calf serum (FCS) supplemented with DHA and/or AA for 10 days. The astrocytes cultured in medium + FCS had low n‐3 PUFA contents, comparable to those of brain tissue from hamsters fed an n‐3‐deficient diet. We have shown that astrocytes grown in medium supplemented with DHA and/or AA, plus α‐tocopherol to prevent lipid peroxidation, incorporated large amounts of these long‐chain PUFA, so that the n‐6/n‐3 PUFA compositions of the phosphatidylethanolamine and phosphatidylcholine, the two main classes of membrane phospholipids, were greatly altered. Astrocytes cultured in medium plus DHA had a more physiological n‐3 status, grew better, and retained their astrocyte phenotype. Thus astrocytes in culture are likely to be physiologically relevant only when provided with adequate DHA. This reliable method of altering membrane phospholipid composition promises to be useful for studying the influence of n‐6/n‐3 imbalance on astrocyte function. © 2003 Wiley‐Liss, Inc.
Oxidative stress induces p53‐mediated apoptosis in glia: p53 transcription‐independent way to die
Authors: Bonini Paolo , Cicconi Simona , Cardinale Alessio , Vitale Cristiana , Serafino Anna Lucia , Ciotti Maria Teresa , Marlier Lionel N.J‐L. 
Published: December 2003

AbstractOxidative stress has been implicated in the pathogenesis of stroke, traumatic brain injuries, and neurodegenerative diseases affecting both neuronal and glial cells in the central nervous system (CNS). The tumor suppressor protein p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. We investigated the role of p53 and related molecular mechanisms that support oxidative stress‐induced apoptosis in glia. For this purpose, we exposed C6 glioma cells and primary cultures of rat cortical astrocytes to an H2O2‐induced oxidative stress protocol followed by a recovery period. We evaluated the effects of pifithrin‐α (PF‐α), which has been reported to protect neurons from ischemic insult by specifically inhibiting p53 DNA‐binding activity. Strikingly, PF‐α was unable to prevent oxidative stress‐induced astrocyte apoptosis. We demonstrate that p53 is able to mediate an apoptotic response by direct signaling at mitochondria, despite its transcriptional activity. The z‐VAD‐fmk‐sensitive apoptotic response requires a caspase‐dependent MDM‐2 degradation, leading to p53 mitochondrial targeting accompanied by cytochrome c release and nucleosomal fragmentation. © 2003 Wiley‐Liss, Inc.
Prenatal infection obliterates glutamate‐related protection against free hydroxyl radicals in neonatal rat brain
Authors: Cambonie Gilles , Hirbec Hélène , Michaud Martine , Kamenka Jean‐Marc , Barbanel Gérard 
Published: December 2003

AbstractPrenatal infection constitutes an important risk factor for brain injury, in both premature and full‐term infants. Unfortunately, as the mechanisms involved are far from understood, no therapeutic strategy emerges to prevent the damage. We tested the hypothesis that administration of lipopolysaccharide (LPS) to gravid female rats enhanced glutamate‐induced oxidative stress in brain of pups. A microdialysis probe was implanted into the striatum of 14‐day‐old animals and the release of hydroxyl radicals (·OH) in the perfusion medium was evaluated. Glutamate promoted a delayed ·OH release in the offspring of dams given LPS, contrasting with the ·OH decreases observed in control animals. A similar response occurred after infusion of (R,S)‐3,5‐dihydroxyphenylglycine (DHPG), a Group I metabotropic glutamate receptor (mGluR) agonist. This response was not consecutive to a remote activation of N‐methyl‐D‐aspartate (NMDA) receptors, as it was unaffected by an NMDA receptor antagonist. Furthermore, the response to NMDA itself decreased in the offspring of dams given LPS. Massive amounts of DHPG, however, likely internalizing the mGlu receptor, still blunted the response to NMDA, as in controls. No quantitative variation occurred in mGluR1, mGluR5, or the NR1 subunit of the NMDA receptor between controls and neonates born from LPS‐treated dams. Direct LPS injection into age‐matched pups, by contrast, affected the response to neither glutamate nor DHPG. These results confirm that normally during perinatal development, the brain is protected from any oxidative stress resulting from excess glutamate, and the results support the hypothesis that maternal infection before delivery may lead to critical brain damage via the release of toxic free radicals. © 2003 Wiley‐Liss, Inc.
The chemokine receptor CXCR4 and not the N‐methyl‐D‐aspartate receptor mediates gp120 neurotoxicity in cerebellar granule cells
Authors: Bachis Alessia , Mocchetti Italo 
Published: December 2003

AbstractThe human immunodeficiency virus type 1 (HIV‐1) glycoprotein gp120 causes neuronal cell death; however, the molecular mechanisms of the neurotoxic effect remain largely unresolved. It has been suggested that gp120 evokes cell death by inducing the release of neurotoxins, including glutamate. The objective of this work was to examine the role of glutamate in gp120‐mediated neurotoxicity. We used as an experimental tool cerebellar granule cells prepared from 8‐day‐old rat cerebella, in which both glutamate and gp120 cause cell death. Cerebellar granule neurons were exposed to gp120 or glutamate alone or in combination with the glutamate receptor antagonist MK801 as well as other antiglutamatergic compounds. Cell viability was measured at various times by using several markers of cell death and apoptosis. MK801, at a concentration that blocked glutamate‐induced neuronal cell death, failed to prevent gp120‐mediated apoptotic cell death. Moreover, interleukin‐10, which has previously been shown to block glutamate toxicity in these neurons, was not neuroprotective against gp120. Because gp120 toxicity is mediated by activation of the chemokine receptor CXCR4, neurons were incubated with the CXCR4 inhibitor AMD3100. This compound prevented gp120‐ but not glutamate‐mediated cell death. These findings suggest that gp120 is toxic to neurons even in the absence of the virus and that the toxic mechanism involves primarily activation of CXCR4 receptor. Therefore, antagonists to the CXCR4 receptor may be more suitable compounds for inhibiting HIV‐1 neurotoxicity. © 2003 Wiley‐Liss, Inc.
Influence of hypnogenic brain areas on wakefulness‐ and rapid‐eye‐movement sleep‐related neurons in the brainstem of freely moving cats
Authors: Mallick Birendra N. , Thankachan Stephen , Islam Fakhrul 
Published: December 2003

AbstractRapid‐eye‐movement (REM) sleep is normally preceded by non‐REM sleep; however, every non‐REM sleep episode is not followed by REM sleep. It has been proposed that, for the regulation of REM sleep, the brain areas modulating waking and non‐REM sleep are likely to communicate with neurons promoting REM sleep. The former has been reported earlier, and in this study the latter has been investigated. Under surgical anaesthesia, cats were prepared for electrophysiological recording of sleep‐wakefulness and electrical stimulation of caudal brainstem as well as preopticoanterior hypothalamic hypnogenic areas. Insulated microwires of 25–32 μm were used to record 52 single neuronal activities from the brainstem along with bipolar electroencephalogram, electromyogram, electrooculogram, and pontogeniculooccipital waves in freely moving, normally behaving cats. The neurons were classified into five groups based on changes in firing rates associated with different sleep‐waking states compared with quiet wakefulness. Thereafter, the responses of these neurons to 1‐Hz stimulation of the two non‐REM sleep‐promoting areas were studied. At the end of experiment, the stimulating and recording sites were histologically identified. It was observed that, among the affected neurons, the caudal brainstem non‐REM sleep‐promoting area excited more REM‐on neurons, whereas the preopticoanterior hypothalamus hypnogenic area inhibited more awake‐active neurons. Thus, the results suggest that, at the single neuronal level, the caudal brainstem non‐REM sleep‐modulating area, rather than the preopticoanterior hypothalamic hypnogenic area in the brain, plays a modulatory role in triggering REM sleep initiation at a certain depth of sleep. © 2003 Wiley‐Liss, Inc.
Maturation of spiking activity in trout retinal ganglion cells coincides with upregulation of Kv3.1‐ and BK‐related potassium channels
Authors: Henne Jutta , Jeserich Gunnar 
Published: December 2003

AbstractDevelopmental changes in membrane excitability and the potassium channel profile were monitored in acutely isolated trout retinal ganglion cells by patch‐clamp recording in combination with single‐cell RT‐PCR. During embryonic development in the egg, a sustained above‐threshold stimulation of ganglion cells elicited in most cases only a single spike response. After hatching, the proportion of multiply spiking cells increased strongly and the ability of spike frequency coding was acquired. This was accompanied by the occurrence of a highly tetraethylammonium (TEA)‐ and quinine‐sensitive delayed rectifier current, which gradually masked a rapidly inactivating A‐type potassium current that was predominant at earlier stages. Pharmacology of the delayed rectifier current closely matched those of recombinant Traw1, a Kv3.1‐related potassium channel in trout. The appearance of this current correlated closely with initial expression of Traw1 and Traw2 channel transcripts, as revealed by multiplex single‐cell RT‐PCR, whereas mRNA, encoding Shaker‐related channel genes in trout (termed Tsha1–Tsha4), were already detectable at early embryonic stages. Iberiotoxin‐sensitive, calcium‐activated potassium currents (BK) were extremely low before hatching, but increased significantly thereafter. These developmental changes in potassium channel expression occurred after the arrival of retinal fibers in the optic tectum and the initiation of synapse formation in the visual center. It is suggested that early expressed Shaker‐related potassium channels could act to influence neuronal differentiation, whereas proper neuronal signaling requires expression of Kv3.1‐ and BK‐related potassium channels. © 2003 Wiley‐Liss, Inc.
Estrogen interacts with the IGF‐1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6‐hydroxdopamine lesions
Authors: Quesada Arnulfo , Micevych Paul E. 
Published: December 2003

AbstractThe most prominent neurochemical hallmark of Parkinson's disease (PD) is the loss of nigrostriatal dopamine (DA). Animal models of PD have concentrated on depleting DA and therapies have focused on maintaining or restoring DA. Within this context estrogen protects against 6‐hydroxdopamine (6‐OHDA) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) lesions of the nigrostriatal DA pathway. Present studies tested the hypothesis that neuroprotective estrogen actions involve activation of the insulin‐like growth factor‐1 (IGF‐1) system. Ovariectomized rats were treated with either a single subcutaneous injection of 17β‐estradiol benzoate or centrally or peripherally IGF‐1. All rats were infused unilaterally with 6‐OHDA into the medial forebrain bundle (MFB) to lesion the nigrostriatal DA pathway. Tyrosine hydroxylase (TH) immunocytochemistry confirmed that rats injected with 6‐OHDA had a massive loss of TH immunoreactivity in both the ipsilateral substantia nigra compacta (60% loss) and the striatum (>95% loss) compared to the contralateral side. Loss of TH immunoreactivity was correlated with loss of asymmetric forelimb movements, a behavioral assay for motor deficits. Pretreatment with estrogen or IGF‐1 significantly prevented 6‐OHDA‐induced loss of substantia nigra compacta neurons (20% loss) and TH immunoreactivity in DA fibers in the striatum (<20% loss) and prevented the loss of asymmetric forelimb use. Blockage of IGF‐1 receptors by intracerebroventricular JB‐1, an IGF‐1 receptor antagonist, attenuated both estrogen and IGF‐1 neuroprotection of nigrostriatal DA neurons and motor behavior. These findings suggest that IGF‐1 and estrogen acting through the IGF‐1 system may be critical for neuroprotective effects of estrogen on nigrostriatal DA neurons in this model of PD. © 2003 Wiley‐Liss, Inc.
The TIMPs tango with MMPs and more in the central nervous system
Authors: Crocker Stephen J. , Pagenstecher Axel , Campbell Iain L. 
Published: December 2003

AbstractThe matrix metalloproteinases (MMPs) are a family of zinc‐dependent extracellular proteases that have been implicated in CNS development and disease. Crucial homeostatic
regulation of MMPs is mediated through the expression and actions of the tissue inhibitors of metalloproteinases (TIMPs). Although the TIMPs are recognized inhibitors of the MMPs, recent
studies have revealed that these proteins also can exhibit biological activities that are distinct from their interactions with or inhibition of the MMPs. With our understanding of the roles of the
TIMPs in the CNS continuously emerging, this review examines the current state of knowledge regarding the multifarious and novel functions of this family of proteins, with particular attention to
their increasing potential in the development, plasticity, and pathology of the CNS. © 2003 Wiley‐Liss, Inc.
An immunohistochemical method that distinguishes free from complexed SNAP‐25
Authors: Xiao Jingnan , Xia Zongping , Pradhan Anuradha , Zhou Qiong , Liu Yuechueng 
Published: December 2003

AbstractSoluble N‐ethylmaleimide‐sensitive fusion protein (NSF) attachment protein receptor (SNARE) complexes composed of target (t‐) SNAREs syntaxin and SNAP‐25 and vesicle SNARE synaptobrevin play an essential role in neurosecretion. It is hypothesized that a transient intermediate complex between the t‐SNAREs is formed during the assembly of the ternary complex. The existence of the t‐SNARE binary complexes in vivo, however, has not been demonstrated. By using an affinity absorption scheme with preformed syntaxin–SNAP‐25 complexes, we isolated antibodies capable of distinguishing free SNAP‐25 from those associated with syntaxin. By semiquantitative immunohistochemistry, we estimated that, in cultured cerebellar neurons, the majority of SNAP‐25 existed as complexes. Compared with the cultured neurons, PC12 cells expressed significantly less syntaxin, and we found that SNAP‐25 was primarily in free forms. In contrast, a PC12 line that stably expressed a recombinant syntaxin showed a marked increase in SNAP‐25 complexes. By using fluorescence resonance energy transfer (FRET) techniques, we observed FRET between cyan fluorescence protein–syntaxin and yellow fluorescence protein–SNAP‐25 fusion proteins expressed in COS‐7 and PC12 cells, suggesting a physiological interaction between syntaxin and SNAP‐25. Our results demonstrate that, unlike what was previously hypothesized, syntaxin and SNAP‐25 exist preferably as stable binary complexes in neurons. These findings offer novel insight into the mechanisms underlying the initiation and regulation of SNARE complex assembly. © 2003 Wiley‐Liss, Inc.
Distribution of sensorin immunoreactivity in the central nervous system of Helix pomatia: Functional aspects
Authors: Casadio Andrea , Fiumara Ferdinando , Sonetti Dario , Montarolo Pier Giorgio , Ghirardi Mirella 
Published: December 2003

AbstractLand snails belonging to the genus Helix are commonly used to study several behaviors and their plasticity at the cellular level. Because the knowledge of sensory neurons in these species is far from being complete, we have investigated the presence and distribution in Helix pomatia central nervous system of the immunoreactivity for sensorin, a peptide specific for mechanosensory neurons in Aplysia. We found that the majority of immunopositive cells were grouped in clusters located in all the central ganglia, except for the pedal ganglion, where only a single large neuron was stained. A symmetrical cluster of stained cells in the cerebral ganglia showed homology with the cerebral J clusters in Aplysia. Most of the somata of these Helix cerebral clusters send their axons in the ipsilateral cerebropedal connective and lip nerves and make monosynaptic connections with cells located in a medial adjacent cluster. This monosynaptic circuit can be reestablished in culture, where it shows homosynaptic depression as it does in the ganglionic preparation. © 2003 Wiley‐Liss, Inc.
Inhibition of histone deacetylation enhances the neurotoxicity induced by the c‐terminal fragments of amyloid precursor protein
Authors: Kim Hye‐Sun , Kim Eun‐Mee , Kim Na‐Jung , Chang Keun‐A , Choi Yoori , Ahn Kwang‐Woo , Lee Jun‐Ho , Kim Seonghan , Park Cheol Hyoung , Suh Yoo‐Hun 
Published: December 2003

AbstractThe AICD (APP intracellular Domain) and C31, caspase‐cleaved C‐terminal fragment of APP, have been found in Alzheimer's disease (AD) patients' brains and have been reported to induce apoptosis in neuronal cells. In recent, the C‐terminal fragments of amyloid precursor protein (APP‐CTs) have been reported to form a complex with Fe65 and the histone acetyltransferase Tip60 and are thought to be involved in gene transcription. In this study, based on the hypothesis that APP‐CTs might exert neurotoxicity by inducing some gene transcription, we investigated the effects of APP‐CTs on histone acetylation which indicates that transcription is actively going on and also on the relationship between histone acetylation and the cytotoxicity induced by APP‐CTs in nerve growth factor (NGF)‐differentiated PC12 cells and rat primary cortical neurons. Here we demonstrate that the expression of APP‐CTs [C31, AICD (C59) and C99] induces increases in acetylation of histone 3 and histone 4 and that treatment with sodium butyrate, an inhibitor of histone deacetylase, significantly enhances the cytotoxicity induced by APP‐CTs. The acetylation of histone plays an important role in allowing regulatory proteins to access DNA and is likely to be a major factor in the regulation of gene transcription. Taken together, our results suggest that APP‐CTs exert neurotoxicity by transcription‐dependent mechanisms and this might contribute to the pathogenesis of AD. © 2003 Wiley‐Liss, Inc.
Multisensory intervention improves physical growth and illness rates in Korean orphaned newborn infants
Authors: Kim Tae Im , Shin Yeong Hee , White‐Traut Rosemary C. 
Published: December 2003

AbstractThe purpose of this study was to evaluate the effectiveness of a multisensory intervention on the physical growth and health of Korean orphaned infants. Fifty‐eight full‐term infants were randomly assigned to a control (n = 28) or an experimental (n = 30) group within 14 days postbirth. In addition to receiving the routine orphanage care, infants in the experimental group received 15 min of auditory (female voice), tactile (massage), and visual (eye‐to‐eye contact) stimulation twice a day, 5 days a week, for 4 weeks. Compared to the control group, the experimental group had gained significantly more weight and had larger increases in length and head circumference after the 4‐week intervention period and at 6 months of age. In addition, the experimental group had significantly fewer illnesses and clinic visits. These data demonstrate that multisensory intervention in conjunction with human/social contact may be effective in facilitating growth for newborn infants placed in orphanages. © 2003 Wiley‐Liss, Inc. Res Nurs Health 26:424–433, 2003