bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐ or post‐training injection of buspirone impaired retention in the inhibitory avoidance task: involvement of amygdala 5‐HT1A receptors
Authors: Liang K. C. 
Published: March 2003

AbstractThe present study investigated the effect of buspirone on memory formation in an aversive learning task. Male Wistar rats were trained on the inhibitory avoidance task and tested for retention 1 day after training. They received peripheral or intra‐amygdala administration of buspirone or other 5‐HT1A drugs either before or after training. Results indicated that pretraining systemic injections of buspirone caused a dose‐dependent retention deficit; 5.0 mg/kg had a marked effect and 1.0 mg/kg had no effect. Post‐training injections of the drug caused a time‐dependent retention deficit, which was not due to a state‐dependent effect on retrieval. When training in the inhibitory avoidance task was divided into a context‐training phase and a shock‐training phase, buspirone impaired retention only when administered in the shock‐training phase, suggesting that the drug influenced memory processing of affective events. Further results indicated that post‐training intra‐amygdala infusion of buspirone or the 5‐HT1A agonist 8‐hydroxy‐di‐n‐propylaminotetralin (8‐OH‐DPAT) caused a time‐dependent and dose‐dependent retention deficit. Post‐training intra‐amygdala infusion of the 5‐HT1A antagonist WAY100635 (N‐(2‐(4‐(2‐methoxyphenyl)‐1‐piperazinyl)‐N‐(2‐pyridyl) cyclohexane carboxamine maleate) attenuated the memory‐impairing effects of buspirone. These findings suggest that buspirone may modulate memory storage processes in the inhibitory avoidance task through an action on amygdaloid 5‐HT1A receptors.
ARNT2, a transcription factor for brain neuron survival?
Authors: Drutel Guillaume , Héron Anne , Kathmann Markus , Gros Claude , Macé Séverine , Plotkine Michel , Schwartz Jean‐Charles , Arrang Jean‐Michel 
Published: March 2003

AbstractThe processes responsible for the limited ability to divide and long survival of neurons are not well understood but may involve aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a recently identified protein, apparently belonging to the basic helix–loop–helix superfamily of transcription factors, which is expressed almost exclusively in brain during the whole lifetime. In agreement, we show, in the rat, that ARNT2 immunoreactivity could be observed only within nuclei of brain neurons and of dividing and neuronal PC12 cells, a localization consistent with a role in transcription regulation. Cell death elicited either by focal ischaemia in brain or oxidative stress in PC12 cells was largely preceded by an almost complete suppression of ARNT2 expression. In contrast, when PC12 cell cycle progression was impaired, ARNT2 expression was enhanced. Finally, the downregulation of ARNT2 levels induced by antisense oligonucleotides prevented PC12 cell proliferation and induced apoptosis. These observations support the hypothesis that ARNT2 is a neuronal transcription factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival.
Presence of a reduced opioid response in interleukin‐6 knock out mice
Authors: Bianchi Mauro , Maggi Roberto , Pimpinelli Federica , Rubino Tiziana , Parolaro Daniela , Poli Valeria , Ciliberto Gennaro , Panerai Alberto E. , Sacerdote Paola 
Published: March 2003

AbstractCytokines are known to influence neuronal functions. The purpose of this study was to investigate the putative role of the cytokine interleukin‐6 (IL‐6) in the pathways involved in opioid‐mediated responses, by using IL‐6‐deficient mice. We reported that with a thermal stimulus IL‐6‐knock‐out (IL‐6KO) mice presented nociceptive thresholds similar to those measured in their controls. However, they showed a reduced analgesic response both to the restraint stress and to the administration of low doses of morphine. Hypothalamic levels of the opioid peptide β‐endorphin were significantly higher in IL‐6KO mice than they were in their controls. The development of tolerance to the analgesic effect of morphine was more rapid in IL‐6‐deficient mice than in wild‐type controls. Binding experiments showed that the number of opioid receptors in the midbrain, but not in the hypothalamus, decreased in IL‐6KO mice. Autoradiographic binding analysis revealed that the density of μ receptors diminished while the δ‐opioid receptors did not. These results suggest that IL‐6 is necessary for a correct development of neuronal mechanisms involved in the response to both endogenous and exogenous opiates.
Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord
Authors: Jeffery N. D. , Crang A. J. , O'Leary M. T. , Hodge S. J. , Blakemore W. F. 
Published: March 2003

AbstractGlial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam‐walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X‐irradiation; in the other, male glial cells were transplanted into nonirradiated female receipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal.
Long‐lasting substance‐P‐mediated modulation of NMDA‐induced rhythmic activity in the lamprey locomotor network involves separate RNA‐ and protein‐synthesis‐dependent stages
Authors: Parker David , Grillner Sten 
Published: March 2003

AbstractBath application of the tachykinin neuropeptide substance P (1 μm) for 10 min causes long‐lasting (> 24 h) modulation of the frequency and regularity of NMDA‐evoked locomotor bursts in the lamprey. The change in burst frequency has an induction phase (< 2 h), which depends on the potentiation of NMDA responses and an increase in intracellular calcium levels, and a maintenance phase (> 2 h), that is blocked by translational protein synthesis inhibitors. Here, the maintenance phase has been examined further. Unlike translation inhibitors, the transcription inhibitors actinomycin D and 5,6‐dichlorobenzimidazole riboside (DRB) failed to reverse the change in burst frequency 2–3 h after substance P application, suggesting that the protein synthesized at this time does not require de novo RNA synthesis. Transcription inhibitors, however, reversed the change in burst frequency 15–24 h after substance P application, as did brefeldin A, which disrupts the Golgi complex and thus interferes with the post‐translational transport of proteins. The change in burst regularity was unaffected by transcription or translation inhibitors, but was partially reversed by protein kinase A inhibitors applied 2.5–8 h after substance P. The glycoprotein synthesis inhibitor 2‐deoxygalactose did not affect the changes in burst frequency or burst regularity. These results suggest that there are two phases to the maintenance of the change in burst frequency: an intermediate protein‐, but not RNA‐, synthesis‐dependent phase, and a final RNA‐synthesis‐dependent phase. The change in burst regularity is protein‐synthesis‐independent, but may depend on activation of protein kinase A for at least 8 h after substance P application.
Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle
Authors: Rosenblad Carl , Kirik Deniz , Devaux Brigitte , Moffat Barbara , Phillips Heidi S. , Björklund Anders 
Published: March 2003

AbstractBoth glial cell line‐derived neurotrophic factor (GDNF) and its recently discovered congener, neurturin (NTN), have been shown to excert neuroprotective effects on lesioned nigral dopamine (DA) neurons when administered at the level of the substantia nigra. In the present study, we have explored the relative in vivo potency of these two neurotrophic factors using two alternative routes of administration, into the striatum or the lateral ventricle, which may be more relevant in a clinical setting. In rats subjected to an intrastriatal (IS) 6‐hydroxydopamine (6‐OHDA) lesion, GDNF and NTN were injected every third day for 3 weeks starting on the day after the 6‐OHDA injection. GDNF provided almost complete (90–92%) protection of the lesioned nigral DA neurons after both IS and intracerebroventricular (ICV) administration. NTN, by contrast, was only partially effective after IS injection (72% sparing) and totally ineffective after ICV injection. Although the trophic factor injections protected the nigral neurons from lesion‐induced cell death, the level of expression of the phenotypic marker, tyrosine hydroxylase (TH), was markedly reduced in the rescued cell bodies. The extent of 6‐OHDA‐induced DA denervation in the striatum was unaffected by both types of treatment; consistent with this observation, the high rate of amphetamine‐induced turning seen in the lesioned control animals was unaltered by either GDNF or NTN treatment. In the GDNF‐treated animals, and to a lesser extent also after IS NTN treatment, prominent axonal sprouting was observed within the globus pallidus, at the level where the lesioned nigrostriatal axons are known to end at the time of onset of the neurotrophic factor treatment. The results show that GDNF is highly effective as a neuroprotective and axon growth‐stimulating agent in the IS 6‐OHDA lesion model after both IS and ICV administration. The lower efficacy of NTN after IS, and particularly ICV, administration may be explained by the poor solubility and diffusion properties at neutral pH.
Mutual regulation between the intercellular messengers nitric oxide and brain‐derived neurotrophic factor in rodent neocortical neurons
Authors: Xiong Huabao , Yamada Kiyofumi , Han Daikenn , Nabeshima Toshitaka , Enikolopov Grigori , Carnahan Josette , Nawa Hiroyuki 
Published: March 2003

AbstractThe diffusible factors, nitric oxide (NO) and brain‐derived neurotrophic factor (BDNF) are both suggested to be intercellular messengers that have similar synaptic activities and developmental influences in the brain. In the present study, we have analysed their mutual regulation with respect to their production in rodent neocortical neurons. Some of the cultured rat neocortical neurons exhibited immunoreactivity for both neuronal NO synthase (NOS) and the BDNF receptor trkB. Neuronal NOS appeared to be activated autonomously and produced NO in culture as monitored by nitrite accumulation. Inhibition of the endogenous NO production in culture by a NOS inhibitor, NG‐monomethyl‐l‐arginine (NMMA), enhanced basal expression of BDNF mRNA and protein. Similarly, cerebroventricular administration of another NOS inhibitor, N‐ω‐nitro‐l‐arginine methylester (l‐NAME), but not d‐NAME or saline, increased BDNF content in the neocortex. In the opposite direction, however, BDNF appeared to function as a positive regulator for NO synthesis. Addition of BDNF upregulated the neuronal NOS expression as well as NO production in neocortical culture. In agreement, BDNF knock‐out mice exhibited significant impairment of neuronal NOS expression in the neocortex. Taken together, these observations suggest that the trans‐synaptic signalling molecules, NO and BDNF, influence the production of each other and mutually regulate the strength of their intercellular communications.
A novel P0 glycoprotein transgene activates expression of lacZ in myelin‐forming Schwann cells
Authors: Feltri M. Laura , D'Antonio Maurizio , Quattrini Angelo , Numerato Rita , Arona Marta , Previtali Stefano , Chiu Shing‐Yan , Messing Albee , Wrabetz Lawrence 
Published: March 2003

AbstractP0 glycoprotein, the most abundant protein in peripheral nerve, is expressed specifically in the Schwann cell lineage. Upstream of the rat P0 gene 1.1 kb of DNA can activate expression of cDNAs specifically in Schwann cells in transgenic mice. However, the expression of P0 promoter‐based transgenes has been inconsistent. As much as 9 kb of 5′ flanking sequence fused to lacZ never yielded detectable levels of β‐galactosidase in multiple lines of mice. We describe transgenic mice that express lacZ in peripheral nerve, using the complete mouse P0 gene, including 6 kb of 5′ flanking sequence, all exons and introns, and the natural polyadenylation signal. This vector activated lacZ expression specifically in cultured Schwann cells, and myelin‐forming Schwann cells in four out of six transgenic lines. Transgene expression paralleled that of the endogenous P0 gene, both during development and after Wallerian degeneration. lacZ expression was lower than endogenous P0 expression, and was not detected in neural crest or Schwann cell precursors, where low levels of P0 mRNA are present. However, when the same vector contained a small myc tag instead of the 3.2‐kb lacZ insert, the resulting transgenic mRNA was expressed at levels comparable to endogenous P0 mRNA. These data suggest that intragenic or 3′ flanking sequences are necessary to generate the remarkable levels of endogenous P0 gene expression.
Region‐dependent difference in the sleep‐promoting potency of an adenosine A2A receptor agonist
Authors: Satoh Shinsuke , Matsumura , Hitoshi , Koike Nobuyo , Tokunaga , Yoshimitsu , Maeda Toshihiro , Hayaishi Osamu 
Published: March 2003

AbstractThe present study has demonstrated that the sleep‐promoting potency of 2‐[p‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A2A receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep–wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pons and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non‐rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680‐inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep‐promoting effect.
Neuronal and behavioural abnormalities in striatal function in DARPP‐32‐mutant mice
Authors: Hiroi Noboru , Fienberg Allen A. , Haile Colin N. , Alburges Mario , Hanson Glen R. , Greengard Paul , Nestler Eric J. 
Published: March 2003

AbstractWe investigated the role of the protein phosphatase inhibitor, dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa (DARPP‐32), in the expression of striatal neuropeptides and in biochemical and behavioural responses to repeated cocaine administration, using DARPP‐32 knock‐out mice. The striatum of DARPP‐32‐mutant mice showed heightened substance‐P‐like immunoreactivity, but normal levels of other neuropeptides. Repeated cocaine administration increased levels of ΔFosB, a Fos family transcription factor, in the striatum of wild‐type mice, and this increase was abolished in DARPP‐32‐mutant mice. Cocaine (20 mg/kg) acutely induced the same level of locomotor activity in the mutant and wild‐type mice, but the mutants showed a higher rate of locomotor sensitization to repeated cocaine exposures. These data show that DARPP‐32 is involved in regulating substance P expression in the striatonigral pathway, and in biochemical and behavioural plasticity with chronic administration of cocaine.
Acetylcholine synthesis and quantal release reconstituted by transfection of mediatophore and choline acetyltranferase cDNAs
Authors: Bloc Alain , Bugnard Elisabeth , Dunant Yves , Falk‐Vairant Jean , Israël Maurice , Loctin Françoise , Roulet Emmanuelle 
Published: March 2003

AbstractNeuroblastoma N18TG‐2 cells cannot synthesize or release acetylcholine (ACh), and do not express proteins involved in transmitter storage and vesicle fusion. We restored some of these functions by transfecting N18TG‐2 cells with cDNAs of either rat choline acetyltransferase (ChAT), or Torpedo mediatophore 16‐kDa subunit, or both. Cells transfected only with ChAT synthesized but did not release ACh. Cells transfected only with mediatophore expressed Ca2+‐dependent ACh release provided they were previously filled with the transmitter. Cell lines produced after cotransfection of ChAT and mediatophore cDNAs released the ACh that was endogenously synthesized. Synaptic‐like vesicles were found neither in native N18TG‐2 cells nor in ChAT‐mediatophore cotransfected clones, where all the ACh content was apparently cytosolic. Furthermore, restoration of release did not result from enhanced ACh accumulation in intracellular organelles consecutive to enhanced acidification by V‐ATPase, as Torpedo 16 kDa transfection did not increase, but decreased the V‐ATPase‐driven proton transport. Using ACh‐sensitive Xenopus myocytes for real‐time recording of evoked release, we found that cotransfected cells released ACh in a quantal manner. We compared the quanta produced by ChAT‐mediatophore cotransfected clones to those produced by clones transfected with mediatophore alone (artificially filled with ACh). The time characteristics and quantal size of currents generated in the myocyte were the same in both conditions. However, cotransfected cells released a larger proportion of their initial ACh store. Hence, expression of mediatophore at the plasma membrane seems to be necessary for quantal ACh release; the process works more efficiently when ChAT is operating as well, suggesting a functional coupling between ACh synthesis and release.
Neuronal correlates of vestibulo‐ocular reflex adaptation in the alert guinea‐pig
Authors: Serafin Mauro , Ris Laurence , Bernard Patrick , Muhlethaler Michel , Godaux Emile , Vidal Pierre‐Paul 
Published: March 2003

AbstractThe spiking behaviour of 66 second‐order vestibular neurons was studied in alert, chronically prepared guinea‐pigs during the horizontal vestibulo‐ocular reflex (VOR). Among the 66 studied neurons, seven were held long enough (> 1 h) to compare their spiking behaviour before and after a training procedure inducing a decrease in the gain of the VOR. When tested in darkness following adaptation, five of them showed a significant decrease of their sensitivity to head rotation. However, the resting discharge of these five neurons remained unchanged. This suggests that VOR adaptation is mediated not only by changes in synaptic efficacities but also by modifications in the spike generator which transforms synaptic inputs into a pattern of action potentials.
Lithium‐pilocarpine‐induced status epilepticus produces necrotic neurons with internucleosomal DNA fragmentation in adult rats
Authors: Fujikawa Denson G. , Shinmei Steve S. , Cai Baiyuan 
Published: March 2003

AbstractProlonged and continuous epileptic seizures [status epilepticus (SE)] produce a widespread pattern of neuronal death, primarily in limbic brain regions. Because it has been suggested that seizure‐induced neuronal death may be apoptotic in nature, we tested the hypothesis that lithium‐pilocarpine‐induced status epilepticus (LPCSE) produces apoptotic neurons. LPCSE lasting 3 h was induced in male Wistar rats which were allowed to recover for 24 or 72 h before perfusion‐fixation. Neuronal death was assessed by light microscopy with the haematoxylin‐and‐eosin stain (H&E), with in situ DNA nick‐end labelling (TUNEL stain), by electron microscopy, and by agarose gel electrophoresis of DNA extracted from vulnerable brain regions. Ultrastructurally, acidophilic neurons identified with H&E were dark, shrunken and necrotic in appearance, exhibiting pyknotic nuclei, irregular, dispersed chromatin clumps and cytoplasmic vacuolization. No cells with apoptotic features were seen. Acidophilic neurons were found in 21 out of 23 brain regions examined, and comprised 26–45% of the total number of neurons examined. A subset of these neurons (< 10% of the total number of neurons) were TUNEL‐positive at 72 h, but not 24 h, after SE. Internucleosomal DNA cleavage (DNA ‘laddering’) was found in the six brain regions examined ultrastructurally 24 and 72 h after SE. These results indicate that, in adult rats, LPCSE produces neuronal injury with the appearance of necrosis rather than apoptosis. The necrotic neurons show nuclear pyknosis, chromatin condensation and internucleosomal DNA fragmentation, confirming the nonspecificity of these nuclear changes. Internucleosomal DNA cleavage and other programmed cell death mechanisms can be activated by SE in neurons which become necrotic.