bluuebunny/crossref_metadata_2025_split huggingface dataset:
The remyelinating potential andin vitrodifferentiation of MOG‐expressing oligodendrocyte precursors isolated from the adult rat CNS
Authors: Crang A. J. , Gilson J. M. , Li W.‐W. , Blakemore W. F. 
Published: September 2004

AbstractThere is a long‐standing controversy as to whether oligodendrocytes may be capable of cell division and thus contribute to remyelination. We recently published evidence that a subpopulation of myelin oligodendrocyte glycoprotein (MOG)‐expressing cells in the adult rat spinal cord co‐expressed molecules previously considered to be restricted to oligodendrocyte progenitors [G. Liet al. (2002)Brain Pathol., 12, 463–471]. To further investigate the properties of MOG‐expressing cells, anti‐MOG‐immunosorted cells were grown in culture and transplanted into acute demyelinating lesions. The immunosorting protocol yielded a cell preparation in which over 98% of the viable cells showed anti‐MOG‐ and O1‐immunoreactivity; 12–15% of the anti‐MOG‐immunosorted cells co‐expressed platelet‐derived growth factor alpha receptor (PDGFRα) or the A2B5‐epitope. When cultured in serum‐free medium containing EGF and FGF‐2, 15–18% of the anti‐MOG‐immunosorted cells lost anti‐MOG‐ and O1‐immunoreactivity and underwent cell division. On removal of these growth factors, cells differentiated into oligodendrocytes, or astrocytes and Schwann cells when the differentiation medium contained BMPs. Transplantation of anti‐MOG‐immunosorted cells into areas of acute demyelination immediately after isolation resulted in the generation of remyelinating oligodendrocytes and Schwann cells. Our studies indicate that the adult rat CNS contains a significant number of oligodendrocyte precursors that express MOG and galactocerebroside, molecules previously considered restricted to mature oligodendrocytes. This may explain why myelin‐bearing oligodendrocytes were considered capable of generating remyelinating cells. Our study also provides evidence that the adult oligodendrocyte progenitor can be considered as a source of the Schwann cells that remyelinate demyelinated CNS axons following concurrent destruction of oligodendrocytes and astrocytes.
Microstimulation of V1 input layers disrupts the selection and detection of visual targets by monkeys
Authors: Slocum Warren M. , Tehovnik Edward J. 
Published: September 2004

AbstractElectrical microstimulation delivered to primary visual cortex (V1) concurrently with the presentation of visual targets interferes with the selection of these targets. To determine the source of this interference, we stimulated the visual input layers of V1 as rhesus monkeys generated saccadic eye movements to visual targets presented at and outside the receptive field of the stimulated neurons. Columns of cells in V1 innervated by the left and right eye are segregated according to eye dominance, such that cells within a column respond best to visual stimuli presented to the ocular dominant eye. Interference was maximal when targets were presented to the ocular dominant eye, moderate when presented to the ocular inferior eye, and negligible when presented to both eyes. Thus, electrical microstimulation of the visual input layers of V1 disrupts the flow of visual information along the geniculostriate pathway. Knowing how electrical stimulation of V1 affects visual behaviour is necessary when using monkeys to develop a visual prosthesis for the blind.
Metabotropic glutamate receptor 5 localized in the limbic forebrain is critical for the development of morphine‐induced rewarding effect in mice
Authors: Aoki Takeshi , Narita Minoru , Shibasaki Masahiro , Suzuki Tsutomu 
Published: September 2004

AbstractThe aim of the present study was to clarify the role of the metabotropic glutamate 5 (mGlu5) receptor subtype in the development of rewarding effect induced by a prototypical µ‐opioid receptor agonist morphine in the mouse. In the conditioned place preference paradigm, intracerebroventricular (i.c.v.) administration of a selective mGlu5 receptor antagonist, 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP), attenuated the morphine‐induced rewarding effects. Using immunoblot analysis, we confirmed that the increased level of protein kinase Cγ (PKCγ) isoform was observed in the limbic forebrain of ICR mice conditioned with morphine. Here we found for the first time that the treatment with MPEP significantly inhibited the up‐regulation of PKCγ isoform in the limbic forebrain of mice showing the significant place preference. Furthermore, it should be mentioned that the protein level of mGlu5 was significantly increased in membrane preparations of the limbic forebrain obtained from morphine‐conditioned mice compared to those from saline‐conditioned mice. As well as the result from the immunoblot analysis, we demonstrated using the receptor binding assay that the number of mGlu5 receptors in the mouse limbic forebrain was significantly increased by morphine conditioning. The present data provide direct evidence that the activation of mGlu5 receptor linked to the increased PKCγ isoform in the mouse limbic forebrain is implicated in the development of rewarding effect of morphine.
3β‐20β‐dihydroxy‐5α‐pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone
Authors: Turkmen Sahruh , Lundgren Per , Birzniece Vita , Zingmark Elisabeth , Backstrom Torbjorn , Johansson Inga‐Maj 
Published: September 2004

AbstractAllopregnanolone is a progesterone metabolite and GABA‐A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3β‐hydroxypregnane steroids antagonize allopregnanolone‐induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3β‐20β‐dihydroxy‐5α‐pregnane (UC1011) as a blocker of allopregnanolone‐induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2‐hydroxypropyl‐β‐cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone‐injected group on day 6. Day 3–6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone‐injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3–6), compared to the allopregnanolone‐injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 µm GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA‐A receptor reduce the negative allopregnanolone effect on learning in the water maze.
Mutation of the feh‐1 gene, the Caenorhabditis elegans orthologue of mammalian Fe65, decreases the expression of two acetylcholinesterase genes
Authors: Bimonte Marida , Gianni Davide , Allegra Danilo , Russo Tommaso , Zambrano Nicola 
Published: September 2004

AbstractThe molecular adaptor Fe65 is one of the cytosolic ligands of the Alzheimer's β‐amyloid precursor protein (APP), and this complex is believed to play important roles in mammalian cells. Upon cleavage of APP by specific processing activities, the complex between Fe65 and the APP intracellular domain (AICD) translocates to the nucleus. Experimental evidence suggests that the Fe65‐AICD complex regulates gene transcription. In Caenorhabditis elegans the orthologue of the Fe65 gene, feh‐1, regulates pharyngeal activity. In fact, the rate of pharyngeal contraction is increased following transient or stable suppression of the feh‐1 gene expression. Here we show that the increased contraction rate of the pharynx in feh‐1 mutant worms is associated to decreased acetylcholinesterase activity. The decreased activity is accompanied by reduced expression of ace‐1 and ace‐2 transcripts, coding for the two major acetylcholinesterase activities in the nematode. These results indicate a target of the regulatory mechanisms based on the Fe65‐APP complex that could be relevant for the pathogenesis of Alzheimer's disease.
The induction of behavioural sensitization is associated with cocaine‐induced structural plasticity in the core (but not shell) of the nucleus accumbens
Authors: Li Yilin , Acerbo Martin J. , Robinson Terry E. 
Published: September 2004

AbstractRepeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.
Cysteinyl‐leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys‐LT1 receptors and mitogen‐activated protein kinase pathway
Authors: Ciccarelli Renata , D'Alimonte Iolanda , Santavenere Clara , D'Auro Mariagrazia , Ballerini Patrizia , Nargi Eleonora , Buccella Silvana , Nicosia Folco Simonetta, Giancarlo , Caciagli Francesco , Di Iorio Patrizia 
Published: September 2004

AbstractCysteinyl‐leukotrienes (cys‐LTs), potent mediators in inflammatory diseases, are produced by nervous tissue, but their cellular source and role in the brain are not very well known. In this report we have demonstrated that rat cultured astrocytes express the enzymes (5′‐lipoxygenase and LTC4 synthase) required for cys‐LT production, and release cys‐LTs in resting condition and, to a greater extent, in response to calcium ionophore A23187, 1 h combined oxygen–glucose deprivation or 2‐methyl‐thioATP, a selective P2Y1/ATP receptor agonist. MK‐886, a LT synthesis inhibitor, prevented basal and evoked cys‐LT release. In addition, 2‐methyl‐thioATP‐induced cys‐LT release was abolished by suramin, a P2 receptor antagonist, or by inhibitors of ATP binding cassette proteins involved in cys‐LT release. We also showed that astrocytes express cys‐LT1 and not cys‐LT2 receptors. The stimulation of these receptors by LTD4 activated the mitogen‐activated protein kinase (MAPK) pathway. This effect was: (i) insensitive to inhibitors of receptor‐coupled Gi protein (pertussis toxin) or tyrosine kinase receptors (genistein); (ii) abolished by MK‐571, a cys‐LT1 selective receptor antagonist, or PD98059, a MAPK inhibitor; (iii) reduced by inhibitors of calcium/calmodulin‐dependent kinase II (KN‐93), Ca2+‐dependent and ‐independent (GF102903X) or Ca2+‐dependent (Gö6976) protein kinase C isoforms. LTD4 also increased astrocyte proliferation and glial fibrillary acidic protein content, which are considered hallmarks of reactive astrogliosis. Both effects were counteracted by cell pretreatment with MK‐571 or PD98059. Thus, cys‐LTs released from astrocytes might play an autocrine role in the induction of reactive astrogliosis that, in brain injuries, contributes to the formation of a reparative glial scar.
Rapid assessment of in vivo cholinergic transmission by amperometric detection of changes in extracellular choline levels
Authors: Parikh Vinay , Pomerleau Francois , Huettl Peter , Gerhardt Greg A. , Sarter Martin , Bruno John P. 
Published: September 2004

AbstractConventional microdialysis methods for measuring acetylcholine (ACh) efflux do not provide sufficient temporal resolution to relate cholinergic transmission to individual stimuli or behavioral responses, or sufficient spatial resolution to investigate heterogeneities in such regulation within a brain region. In an effort to overcome these constraints, we investigated a ceramic‐based microelectrode array designed to measure amperometrically rapid changes in extracellular choline as a marker for cholinergic transmission in the frontoparietal cortex of anesthetized rats. These microelectrodes exhibited detection limits of 300 nm for choline and selectivity (> 100 : 1) of choline over interferents such as ascorbic acid. Intracortical pressure ejections of choline (20 mm, 66–400 nL) and ACh (10 and 100 mm, 200 nL) dose‐dependently increased choline‐related signals that were cleared to background levels within 10 s. ACh, but not choline‐induced signals, were significantly attenuated by co‐ejection of the acetylcholinesterase inhibitor neostigmine (Neo; 100 mm). Pressure ejections of drugs known to increase cortical ACh efflux, potassium (KCl; 70 mm, 66, 200 nL) and scopolamine (Scop; 10 mm, 200 nL), also markedly increased extracellular choline signals, which again were inhibited by Neo. Scop‐induced choline signals were also found to be tetrodotoxin‐sensitive. Collectively, these findings suggest that drug‐induced increases in current measured with these microelectrode arrays reflect the oxidation of choline that is neuronally derived from the release and subsequent hydrolysis of ACh. Choline signals assessed using enzyme‐selective microelectrode arrays may represent a rapid, sensitive and spatially discrete measure of cholinergic transmission.
Associative somatodendritic interaction in layer V pyramidal neurons is not affected by the antiepileptic drug lamotrigine
Authors: Berger Thomas , Lüscher Hans‐R. 
Published: September 2004

AbstractThe antiepileptic drug lamotrigine was described to exert its effects on neuronal excitability via voltage‐gated sodium and calcium, as well as hyperpolarization‐activated conductances. In order to define the effects of lamotrigine on the excitability of layer V pyramidal cells of the rat somatosensory cortex we performed patch‐clamp recordings from the soma and dendrite of this major cortical output cell type in acute slices. Voltage‐clamp experiments revealed the blockade of the persistent sodium current by 50–100 µm lamotrigine as well as by 50 µm of the anticonvulsant drug phenytoin. In somatic current‐clamp studies lamotrigine, in a therapeutic concentration range, depolarizes the membrane potential reflecting the activation of the hyperpolarization‐activated current. This depolarization reduces the rheobase and increases the spiking frequency at the onset of the spike train. For long depolarizing current pulses under lamotrigine, however, a use‐dependent block of sodium channels reduces spiking frequency and spike amplitude. The depolarization due to 50–100 µm lamotrigine reduces additionally the critical frequency of back‐propagating spikes necessary to elicit a dendritic calcium action potential. Ten to thirty micromolar lamotrigine, in contrast, did not change the critical frequency. Lamotrigine blocks long‐lasting, high frequent spiking activity due to its use‐dependent sodium channel block, while burst activity is not impaired due to a depolarizing shift of the membrane potential. This drug therefore dampens epileptic activity while leaving the somatodendritic association in layer V pyramidal cells intact.
Cocaine increases medial prefrontal cortical glutamate overflow in cocaine‐sensitized rats: a time course study
Authors: Williams Jason M. , Steketee Jeffery D. 
Published: September 2004

AbstractExcitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague–Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day × 4 days, i.p.) or cocaine (15 mg/kg/day × 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine‐induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine‐induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine‐induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine.
Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice
Authors: Kurrikoff Kaido , Kõks Sulev , Matsui Toshimitsu , Bourin Michel , Arend Andres , Aunapuu Marina , Vasar Eero 
Published: September 2004

AbstractPrevious studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK2 receptor deficient (CCK2 −/−) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK2 −/− mice displayed mechanical hyposensitivity, which was reversed to the level of wild‐type animals after administration of naloxone (0.1–10 mg/kg). On the other hand, injection of L‐365260 (0.01–1 mg/kg), an antagonist of CCK2 receptors, decreased dose‐dependently, mechanical sensitivity in wild‐type mice. The mechanism of reduced mechanical sensitivity in CCK2 −/− mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK2 −/− mice natively expressed higher levels of lumbar CCK1, opioid δ and κ receptors. Next, we found that CCK2 −/− mice did not develop mechanical hyperalgesia in the Bennett's neuropathic pain model. Induction of neuropathy resulted in decrease of lumbar pro‐opiomelanocortin (POMC) gene expression in wild‐type mice, but increase of POMC expression in CCK2 −/− mice. In addition, induction of neuropathy resulted in further increase of opioid δ receptor in CCK2 −/− mice. Gene expression results indicate up‐regulation of opioid system in CCK2 −/− mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.
Binding partners L1 cell adhesion molecule and the ezrin‐radixin‐moesin (ERM) proteins are involved in development and the regenerative response to injury of hippocampal and cortical neurons
Authors: Haas Matilda A. , Vickers James C. , Dickson Tracey C. 
Published: September 2004

AbstractRegeneration of the adult central nervous system may require recapitulation of developmental events and therefore involve the re‐expression of developmentally significant proteins. We have investigated whether the L1 cell adhesion molecule, and its binding partner, the ezrin‐radixin‐moesin (ERM) proteins are involved in the neuronal regenerative response to injury. Hippocampal and cortical neurons were cultured in vitro on either an L1 substrate or poly‐L‐lysine, and ERM and other neuronal proteins were localized immunocytochemically both developmentally and following neurite transection of neurons maintained in long‐term culture. Activated ERM was localized to growth cones up to 7 days in vitro but relatively mature cultures (21 days in vitro) were devoid of active ERM proteins. However, ERM proteins were localized to the growth cones of sprouting neuronal processes that formed several hours after neurite transection. In addition, the L1 substrate, relative to poly‐L‐lysine, resulted in significantly longer regenerative neurites, as well as larger growth cones with more filopodia. Furthermore, neurons derived from the cortex formed significantly longer post‐injury neurite sprouts at 6 h post‐injury than hippocampal derived neurons grown on both substrates. We have demonstrated that L1 and the ERM proteins are involved in the neuronal response to injury, and that neurons derived from the hippocampus and cortex may have different post‐injury regenerative neurite sprouting abilities.
Angiotensin II increases differentiation of dopaminergic neurons from mesencephalic precursors via angiotensin type 2 receptors
Authors: Rodriguez‐Pallares J. , Quiroz C. R. , Parga J. A. , Guerra M. J. , Labandeira‐Garcia J. L. 
Published: September 2004

AbstractIn addition to the well‐known actions of the humoral renin–angiotensin system, all components of this system are present in many tissues, including the brain, and may play a major role in brain development and differentiation. We investigated the possible effects of angiotensin II on the generation of dopaminergic phenotype neurons from proliferating neurospheres of mesencephalic precursors. We observed immunoreactivity for both angiotensin type 1 and type 2 (AT1 and AT2) receptors in the cell aggregates. Double immunolabeling studies revealed that both receptor types are located in neurons and astrocytes. Interestingly, neurons with a dopaminergic phenotype (i.e. tyrosine hydroxylase activity) showed double labeling for AT1 and AT2 receptors although the labeling for AT2 was more intense. Treatment of the neurospheres with angiotensin II (100 nm) during the differentiation period induced a marked increase (about 400%) in the generation of dopaminergic neurons. This was not affected by treatment with the AT1 antagonist ZD 7155 but was blocked by treatment with the AT2 antagonist PD 123319. This suggests that AT2 receptors mediate the stimulatory effect of angiotensin II on the generation of dopaminergic neurons. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the increase in generation of dopaminergic neurons is not due to increased survival or proliferation of dopaminergic cells during treatment with angiotensin and suggested that angiotensin induces increased differentiation of mesencephalic precursors towards the dopaminergic phenotype. Manipulation of the renin–angiotensin system may be useful for increasing production of dopaminergic neurons for transplantation in Parkinson's disease.