bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure resistance in fat‐1 transgenic mice endogenously synthesizing high levels of omega‐3 polyunsaturated fatty acids
Authors: Taha Ameer Y. , Huot Pedro S. P. , Reza‐López Sandra , Prayitno Nita R. , Kang Jing X. , Burnham W. McIntyre , Ma David W. L. 
Published: March 2008

Abstractn‐3 polyunsaturated fatty acids (PUFA), derived from marine oils, have been shown to protect against various neurological diseases. However, very little is known about their potential anticonvulsant properties. The objective of the present study was to determine whether enrichment of brain lipids with n‐3 PUFA inhibits seizures induced by pentylenetetrazol. We demonstrate that increased brain levels of n‐3 PUFA in transgenic fat‐1 male mice, which are capable of de novo synthesis of n‐3 PUFA from n‐6 PUFA, increases latency to seizure onset by 45%, relative to wildtype controls (p = 0.08). Compared with wildtype littermates, transgenic fat‐1 mice have significantly (p < 0.05) higher levels of docosahexaenoic acid and total n‐3 PUFA in brain total lipid extracts and phospholipids. Levels of brain docosahexaenoic acid were positively correlated to seizure latency (p < 0.05). These findings demonstrate that n‐3 PUFA have anticonvulsant properties and suggest the possibility of a novel, non‐drug dietary approach for the treatment of epilepsy.
Age‐related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild‐type mice
Authors: Minkeviciene R. , Ihalainen J. , Malm T. , Matilainen O. , Keksa‐Goldsteine V. , Goldsteins G. , Iivonen H. , Leguit N. , Glennon J. , Koistinaho J. , Banerjee P. , Tanila H. 
Published: March 2008

AbstractWe assessed baseline and KCl‐stimulated glutamate release by using microdialysis in freely moving young adult (7 months) and middle‐aged (17 months) transgenic mice carrying mutated human amyloid precursor protein and presenilin genes (APdE9 mice) and their wild‐type littermates. In addition, we assessed the age‐related development of amyloid pathology and spatial memory impaired in the water maze and changes in glutamate transporters. APdE9 mice showed gradual spatial memory impairment between 6 and 15 months of age. The stimulated glutamate release declined very robustly in 17‐month‐old APdE9 mice as compared to 7‐month‐old APdE9 mice. This age‐dependent decrease in stimulated glutamate release was also evident in wild‐type mice, although it was not as robust as in APdE9 mice. When compared to individual baselines, all aged wild‐type mice showed 25% or greater increase in glutamate release upon KCl stimulation, but none of the aged APdE9 mice. There was an age‐dependent decline in VGLUT1 levels, but not in the levels of VGLUT2, GLT‐1 or synaptophysin. Astrocyte activation as measured by glial acidic fibrillary protein was increased in middle‐aged APdE9 mice. Blunted pre‐synaptic glutamate response may contribute to memory deficit in middle‐aged APdE9 mice.
Simvastatin prevents the inflammatory process and the dopaminergic degeneration induced by the intranigral injection of lipopolysaccharide
Authors: Hernández‐Romero María del Carmen , Argüelles Sandro , Villarán Ruth F. , De Pablos Rocío M. , Delgado‐Cortés María José , Santiago Marti , Herrera Antonio J. , Cano Josefina , Machado Alberto 
Published: March 2008

AbstractAnti‐inflammatory strategies have attracted much interest for their potential to prevent further deterioration of Parkinson’s disease. Recent experimental and clinical evidence indicate that statins – extensively used in medical practice as effective lipid‐lowering agents – have also anti‐inflammatory effects. In this study, we investigated the influence of simvastatin on the degenerative process of the dopaminergic neurons of the rat following intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation that we have previously used as an animal model of Parkinson’s disease. We evaluated TH positive neurons, astroglial, and microglial populations and found that simvastatin prevented the inflammatory processes, as the induction of interleukin‐1β, tumor necrosis factor‐α, and iNOS and the consequent dopaminergic degeneration induced by LPS. Moreover, simvastatin produced the activation of the neurotrophic factor BDNF, along with the prevention of the oxidative damage to proteins. Moreover, it also prevents the main changes produced by LPS on different mitogen‐activated protein kinases, featured as increases of P‐c‐Jun N‐terminal protein kinase, P‐extracellular signal‐regulated kinase, p‐38, and P‐glycogen synthase kinase and the decrease of the promotion of cell survival signals such as cAMP response element‐binding protein and Akt. Our results suggest that statins could delay the progression of dopaminergic degeneration in disorders involving inflammatory processes.
BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice
Authors: Aso Ester , Ozaita Andrés , Valdizán Elsa M. , Ledent Catherine , Pazos Ángel , Maldonado Rafael , Valverde Olga 
Published: March 2008

AbstractStress can cause damage and atrophy of neurons in the hippocampus by deregulating the expression of neurotrophic factors that promote neuronal plasticity. The endocannabinoid system represents a physiological substrate involved in neuroprotection at both cellular and emotional levels. The lack of CB1 receptor alters neuronal plasticity and originates an anxiety‐like phenotype in mice. In the present study, CB1 knockout mice exhibited an augmented response to stress revealed by the increased despair behavior and corticosterone levels showed in the tail suspension test and decreased brain derived neurotrophic factor (BDNF) levels in the hippocampus. Interestingly, local administration of BDNF in the hippocampus reversed the increased despair behavior of CB1 knockout mice, confirming the crucial role played by BDNF on the emotional impairment of these mutants. The neurotrophic deficiency seems to be specific for BDNF as no differences were found in the levels of nerve growth factor and NT‐3, two additional neurotrophic factors. Moreover, BDNF impairment is not related to the activity of its specific tyrosine kinase receptor or the activity of the transcription factor cAMP responsive element binding. These results suggest that the lack of CB1 receptor originates an enhanced response to stress and deficiency in neuronal plasticity by decreasing BDNF levels in the hippocampus that lead to impairment in the responses to emotional disturbances.
Photoreceptor‐specific expression, light‐dependent localization, and transcriptional targets of the zinc‐finger protein Yin Yang 1 in the chicken retina
Authors: Bernard Marianne , Voisin Pierre 
Published: March 2008

AbstractThe zinc‐finger transcription factor Yin Yang 1 (YY1) is a multifunctional protein that plays a critical role in embryonic development. Although it has been shown to play a role in eye development, its expression in the retina was not previously described. Here, we investigated YY1 expression in chicken tissues and we identified the neural retina as one of the tissues with highest YY1 protein levels. Immunohistochemical detection of YY1 in the retina revealed a clear‐cut photoreceptor specificity and day/night differences in the cytoplasmic localization of the protein. YY1 was also present at high concentration in the nuclei of some photoreceptors. Gel‐shift assays indicated YY1 bound to regulatory regions of several genes specifically expressed in photoreceptors. One of these genes, hydroxyindole‐O‐methyltransferase (EC 2.1.1.4), encodes the last enzyme of the melatonin synthesis pathway. Although over‐expression of chicken YY1 was not sufficient to activate the chicken hydroxyindole‐O‐methyltransferase promoter in HEK293 cells, the YY1‐binding site contained in this promoter was clearly required for full transcriptional activity in chicken embryonic retinal cells. These results suggest a role of YY1 in regulating the melatoninergic function of retinal photoreceptors.
Agonist‐ and competitive antagonist‐induced movement of loop 5 on the α subunit of the neuronal α4β4 nicotinic acetylcholine receptor
Authors: Mourot Alexandre , Bamberg Ernst , Rettinger Jürgen 
Published: March 2008

AbstractNeuronal nicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels that rapidly convert a chemical signal into an electrical signal. Although the structure of the nAChR is quite well described, the coupling between agonist binding and channel gating is still under debate. In this study, we probed local conformational transitions on the neuronal α4β4 nAChR by specifically tethering a conformation‐sensitive fluorescent dye on αG98C located on loop 5 (L5), and simultaneously monitoring fluorescence intensity and current after expression inXenopusoocytes. The potency of acetylcholine (ACh) was significantly higher in the cysteine mutant and further increased upon tetramethylrhodamine‐6‐maleimide labeling, suggesting a role of L5 in binding or gating. Structural reorganizations of L5 were shown to occur upon activation, as revealed by the fluorescence intensity increase during ACh exposure. Fluorescence changes were also detected at ACh concentrations lower than needed for current activation, suggesting a movement of L5 for a closed, resting or desensitized state. The competitive antagonist dihydro‐β‐erythroidine also induced a movement of L5 although at concentrations significantly higher than needed for current inhibition. Consequently L5, located inside the lumen of the pentamer, plays a role in both activation and inhibition of the nAChR.
Increased social interaction in mice deficient of the striatal medium spiny neuron‐specific phosphodiesterase 10A2
Authors: Sano Hiromi , Nagai Yumiko , Miyakawa Tsuyoshi , Shigemoto Ryuichi , Yokoi Mineto 
Published: March 2008

AbstractCyclic nucleotide phosphodiesterase 10A (PDE10A) is a member of phosphodiesterase families that degrade cAMP and/or cGMP in distinct intracellular sites. PDE10A has a dual activity on hydrolysis of both cAMP and cGMP, and is prominently expressed in the striatum and the testis. Previous studies suggested that PDE10A is involved in regulation of locomotor activity and potentially related to psychosis, but concrete physiological roles of PDE10A remains elusive yet. In this study, we genetically inactivated PDE10A2, a prominent isoform of PDE10A in the brain, in mice, and demonstrate that PDE10A2 deficiency results in increased social interaction without any major influence on different other behaviors, along with increased levels of striatal cAMP. We also demonstrate that PDE10A2 is selectively distributed in medium spiny neurons, but not interneurons, of the striatal complex. Thus, our results establish a physiological role for PDE10A2 in regulating cAMP pathway and social interaction, and suggest that cAMP signaling cascade in striatal medium spiny neurons might be involved in regulating social interaction behavior in mice.
Dopaminergic differentiation of human neural stem cells mediated by co‐cultured rat striatal brain slices
Authors: Anwar Mohammad Raffaqat , Andreasen Christian Maaløv , Lippert Solvej Kølvraa , Zimmer Jens , Martinez‐Serrano Alberto , Meyer Morten 
Published: March 2008

AbstractProperly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson’s disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic differentiation, we co‐cultured cells from a human neural forebrain‐derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six‐well trays overlying monolayers of hNS1 cells. After 12 days of co‐culture, large numbers of tyrosine hydroxylase (TH)‐immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH‐positive, contrasting a few TH‐positive cells (<1%) in non‐induced areas. The presence of dopamine in the conditioned culture medium was confirmed by HPLC analysis. Interestingly, not all striatal slice cultures induced TH‐expression in underlying hNS1 cells. Common to TH‐inductive cultures was, however, the presence of degenerating, necrotic areas, suggesting that factors released during striatal degeneration were responsible for the dopaminergic induction of the hNS1 cells. Ongoing experiments aim to identify such factors by comparing protein profiles of media conditioned by degenerating (necrotic) versus healthy striatal slice cultures.
Validation of a robust and sensitive method for detecting hydroxyl radical formation together with evoked neurotransmitter release in brain microdialysis
Authors: Freinbichler Wolfhardt , Colivicchi Maria A. , Fattori Manuela , Ballini Chiara , Tipton Keith F. , Linert Wolfgang , Della Corte Laura 
Published: March 2008

AbstractSodium terephthalate was shown to be a new robust and sensitive chemical trap for highly reactive oxygen species (hROS), which lacks the drawbacks of the salicylic acid method. Reaction of the almost non‐fluorescent terephthalate (TA2−) with hydroxyl radicals or ferryl‐oxo species resulted in the stoichiometric formation of the brilliant fluorophor, 2‐hydroxyterephthalate (OH‐TA). Neither hydrogen peroxide nor superoxide reacts in this system. This procedure was validated for determining hROS formation during microdialysis under in vivo conditions as well as by in vitro studies. The detection limit of OH‐TA in microdialysis samples was 0.5 fmol/μL. Derivatization of samples with o‐phthalaldehyde, for amino acid detection, had no effect on OH‐TA fluorescence, which could easily be resolved from the amino acid derivatives by HPLC, allowing determination in a single chromatogram. Use of terephthalate in microdialysis experiments showed the neurotoxin kainate to evoke hROS formation in a dose‐dependent manner. The presence of TA2− in the perfusion fluid did not affect basal or evoked release of aspartate, glutamate, taurine and GABA. Assessment of cell death ‘ex vivo’ showed TA2− to be non‐toxic at concentrations up to 1 mM. The in vitro results in the Fenton system (Fe2+ + H2O2) indicate a mechanism whereby TA2− forms a primary complex with Fe2+ followed by an intramolecular hydroxylation accompanied by intramolecular electron transfer.
Molecular characterization and localization of the RIC‐3 protein, an effector of nicotinic acetylcholine receptor expression
Authors: Castelán Francisco , Castillo Mar , Mulet José , Sala Salvador , Sala Francisco , Domínguez del Toro Eduardo , Criado Manuel 
Published: March 2008

AbstractThe RIC‐3 protein acts as a regulator of acetylcholine nicotinic receptor (nAChR) expression. In Xenopus laevis oocytes the human RIC‐3 (hRIC‐3) protein enhances expression of α7 receptors and abolishes expression of α4β2 receptors. In vitro translation of hRIC‐3 evidenced its membrane insertion but not the role as signal peptide of its first transmembrane domain (TMD). When the TMDs of hRIC‐3 were substituted, its effects on nAChR expression were attenuated. A certain linker length between the TMDs was also needed for α7 expression enhancement but not for α4β2 inhibition. A combination of increased α7 receptor steady state levels, facilitated transport and reduced receptor internalization appears to be responsible for the increase in α7 membrane expression induced by hRIC‐3. Antibodies against hRIC‐3 showed its expression in SH‐SY5Y and PC12 cells and its induction upon differentiation. Immunohistochemistry demonstrated the presence of RIC‐3 in rat brain localized, in general, in places where α7 nAChRs were found.
The intrastriatal injection of thrombin in rat induced a retrograde apoptotic degeneration of nigral dopaminergic neurons through synaptic elimination
Authors: Herrera Antonio J. , De Pablos Rocío M. , Carreño‐Müller Eloisa , Villarán Ruth F. , Venero José L. , Tomás‐Camardiel Mayka , Cano Josefina , Machado Alberto 
Published: March 2008

AbstractWe have performed intrastriatal injection of thrombin and searched for distant effects in the cell body region. In striatum, thrombin produced a slight loss of striatal neurons as demonstrated by neural nuclei immunostaining – a non‐specific neuronal marker – and the expression of glutamic acid decarboxylase 67 mRNA, a specific marker for striatal GABAergic interneurons, the most abundant phenotype in this brain area. Interestingly, striatal neuropil contained many boutons immunostained for synaptic vesicle protein 2 and synaptophysin which colocalize with tyrosine hydroxylase (TH), suggesting a degenerative process with pre‐synaptic accumulation of synaptic vesicles. When we studied the effects on substantia nigra, we found the disappearance of dopaminergic neurons, shown by loss of TH immunoreactivity, loss of expression of TH and dopamine transporter mRNAs, and disappearance of FluoroGold‐labelled nigral neurons. The degeneration of substantia nigra dopaminergic neurons was produced through up‐regulation of cFos mRNA, apoptosis and accumulation of α‐synuclein shown by colocalization experiments. Thrombin effects could be mediated by protease‐activated receptor 4 activation, as protease‐activated receptor 4‐activating peptide mimicked thrombin effects. Our results point out the possible relationship between synapse elimination and retrograde degeneration in the nigral dopaminergic system.
Silencing of the ADNP‐family member, ADNP2, results in changes in cellular viability under oxidative stress
Authors: Kushnir Michal , Dresner Efrat , Mandel Shmuel , Gozes Illana 
Published: March 2008

AbstractActivity‐dependent neuroprotective protein (ADNP) 2 (KIAA0863; ZNF508) gene, a homeobox‐profile containing gene, was identified in a screen for homologous proteins to ADNP. The human ADNP2 contains 1131 amino acid residues with a molecular weight of 122.8 KDa. In silico analysis indicated that ortholgs to ADNP2 exist in different phyla, suggesting that ADNP2 might be evolutionary conserved. Here, we began to explore the molecular and functional characterization of ADNP2. Results showed that the mouse ADNP2 mRNA is ubiquitously expressed in distinct normal tissues with increased expression in the brain, particularly in the cerebral cortex. During development, a relatively high level of ADNP2 gene expression was found in the embryonic mouse brain and was sustained throughout embryogenesis and adulthood. An increase in the mRNA was detected in differentiated P19 neuronal/glial‐like cells as compared with the non‐differentiated cells. To gain insight into ADNP2 function, ADNP2‐deficient cell lines were established by the RNA silencing (small interfering RNA) technology. ADNP2 deficiency significantly changed the toxicity induced by hydrogen peroxide in P19 embryonic carcinoma cells, similar to what would be predicted for ADNP deficiency. These findings represent an initial characterization of ADNP2 and suggest that this gene product may have an important function in brain by playing a role in cellular survival pathways.
Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects ofl‐carnitine
Authors: Silva‐Adaya Daniela , Pérez‐De La Cruz Verónica , Herrera‐Mundo María Nieves , Mendoza‐Macedo Karina , Villeda‐Hernández Juana , Binienda Zbigniew , Ali Syed F. , Santamaría Abel 
Published: March 2008

AbstractExcitotoxicity and disrupted energy metabolism are major events leading to nerve cell death in neurodegenerative disorders. These cooperative pathways share one common aspect: triggering of oxidative stress by free radical formation. In this work, we evaluated the effects of the antioxidant and energy precursor, levocarnitine (l‐CAR), on the oxidative damage and the behavioral, morphological, and neurochemical alterations produced in nerve tissue by the excitotoxin and free radical precursor, quinolinic acid (2,3‐pyrindin dicarboxylic acid; QUIN), and the mitochondrial toxin, 3‐nitropropionic acid (3‐NP). Oxidative damage was assessed by the estimation of reactive oxygen species formation, lipid peroxidation, and mitochondrial dysfunction in synaptosomal fractions. Behavioral, morphological, and neurochemical alterations were evaluated as markers of neurotoxicity in animals systemically administered withl‐CAR, chronically injected with 3‐NP and/or intrastriatally infused with QUIN. At micromolar concentrations,l‐CAR reduced the three markers of oxidative stress stimulated by both toxins alone or in combination.l‐CAR also prevented the rotation behavior evoked by QUIN and the hypokinetic pattern induced by 3‐NP in rats. Morphological alterations produced by both toxins (increased striatal glial fibrillary acidic protein‐immunoreactivity for QUIN and enhanced neuronal damage in different brain regions for 3‐NP) were reduced byl‐CAR. In addition,l‐CAR prevented the synergistic action of 3‐NP and QUIN to increase motor asymmetry and depleted striatal GABA levels. Our results suggest that the protective properties ofl‐CAR in the neurotoxic models tested are mostly mediated by its characteristics as an antioxidant agent.
AMP‐activated protein kinase phosphorylation in brain is dependent on method of killing and tissue preparation
Authors: Scharf Matthew T. , Mackiewicz Miroslaw , Naidoo Nirinjini , O’Callaghan James P. , Pack Allan I. 
Published: March 2008

AbstractAMP‐activated protein kinase (AMPK) is activated when the catalytic α subunit is phosphorylated on Thr172 and therefore, phosphorylation of the α subunit is used as a measure of activation. However, measurement of α subunit of AMPK (α‐AMPK) phosphorylation in vivo can be technically challenging. To determine the most accurate method for measuring α‐AMPK phosphorylation in the mouse brain, we compared different methods of killing and tissue preparation. We found that freeze/thawing samples after homogenization on ice dramatically increased α‐AMPK phosphorylation in mice killed by cervical dislocation. Killing of mice by focused microwave irradiation, which rapidly heats the brain and causes enzymatic inactivation, prevented the freeze/thaw‐induced increase in α‐AMPK phosphorylation and similar levels of phosphorylation were observed compared with mice killed with cervical dislocation without freeze/thawing of samples. Sonication of samples in hot 1% sodium dodecyl sulfate blocked the freeze/thaw‐induced increase in α‐AMPK phosphorylation, but phosphorylation was higher in mice killed by cervical dislocation compared with mice killed by focused microwave irradiation. These results demonstrate that α‐AMPK phosphorylation is dependent on method of killing and tissue preparation and that α‐AMPK phosphorylation can increase in a manner that does not reflect biological alterations.