bluuebunny/crossref_metadata_2025_split huggingface dataset:
The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats
Authors: Huang W. L. , George K. J. , Ibba V. , Liu M. C. , Averill S. , Quartu M. , Hamlyn P. J. , Priestley J. V. 
Published: January 2007

AbstractStudies of spinal cord injury using contusion (impact) injury paradigms have shown that neuronal death is an acute event that is largely over within 24 h. However, much less is known about cell death following compression injury, despite compression being a key component of natural spinal injuries. We have therefore used neuronal nuclei (NeuN) immunostaining to examine the spatiotemporal pattern of neuronal loss after static compression injury in adult rats. 3D reconstruction was used to reveal the full effect of the injury. Neuronal loss at the injury epicentre, assessed by NeuN immunostaining, amounted to 44% at 1 day but increased to 73% at 3 days and 81% at 1 month. Neuronal loss was also seen 5 mm rostral and caudal to the epicentre, but was not significant until 3 days. NeuN loss was greatest in the ventral horns and in the intermediate grey matter, with the lateral dorsal horns relatively spared. Cystic cavities formed after injury, but were not evident until 4 weeks and were small in size. In contrast to the slow profile of neuronal loss, the compression injury also evoked a transient expression of activating transcription factor‐3 (ATF3) and activated c‐Jun in neurons. ATF3 expression peaked at 3 days and declined at 7 days. Our spatiotemporal analysis of compression injury shows that neuronal loss is much more protracted than in contusion injury, and highlights the potential for neuroprotective strategies. This study is also the first indication of ATF3 involvement in spinal cord injury.
Time‐course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6‐hydroxydopamine in the rat: new clues from an old model
Authors: Blandini Fabio , Levandis Giovanna , Bazzini Eleonora , Nappi Giuseppe , Armentero Marie‐Therese 
Published: January 2007

AbstractDespite the progressive development of innovative animal models for Parkinson's disease, the intracerebral infusion of neurotoxin 6‐hydroxydopamine (6‐OHDA) remains the most widely used means to induce an experimental lesion of the nigrostriatal pathway in the animal, due to its relatively low complexity and cost, coupled with the high reproducibility of the lesion obtained. To gain new information from such a classic model, we studied the time‐course of the nigrostriatal damage, metabolic changes in the basal ganglia nuclei (cytochrome oxidase activity) and behavioural modifications (rotational response to apomorphine) following unilateral injection of 6‐OHDA into the corpus striatum of rat, over a 4‐week period. Striatal infusion of 6‐OHDA caused early damage of dopaminergic terminals, followed by a slowly evolving loss of dopaminergic cell bodies in the substantia nigra pars compacta, which became apparent during the second week post‐injection and peaked at the 28th day post‐infusion; the rotational response to apomorphine was already present at the first time point considered (Day 1), and remained substantially stable throughout the 4‐week period of observation. The evolution of the nigrostriatal lesion was accompanied by complex changes in the metabolic activity of the other basal ganglia nuclei investigated (substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and subthalamic nucleus), which led, ultimately, to a generalized, metabolic hyperactivity, ipsilaterally to the lesion. However, peculiar patterns of metabolic activation, or inhibition, characterized the post‐lesional responses of each nucleus, in the early and intermediate phases, with peculiar response profiles that varied closely related to the functional position occupied within the basal ganglia circuitry.
Dissociation of sustained attention from central executive functions: local activity and interregional connectivity in the theta range
Authors: Sauseng P. , Hoppe J. , Klimesch W. , Gerloff C. , Hummel F. C. 
Published: January 2007

AbstractHuman brain oscillatory activity was analysed in the electroencephalographic theta frequency range (4–7 Hz) while subjects executed complex sequential finger movements with varying task difficulty and memory load. Local frontal‐midline theta activity was associated with the general level of cognitive demand, with the highest amplitudes in the most demanding condition. Using low‐resolution electromagnetic tomography analysis (LORETA), this theta activity was localized in the anterior cingulate gyrus including the cingulate motor area. These results suggest that local theta activity in the anterior cingulate gyrus represents correlates of an attentional system that allocate cognitive resources. In addition, interregional connectivity in the theta frequency range was modulated by memory‐related executive functions independently of task difficulty. Connectivity analyses revealed a more distributed long‐range network including frontal and parietal cortices during execution of novel compared with well‐trained finger movement sequences. Thus, these results are compatible with a model in which theta long‐range coupling indicates integration of sensory information into executive control components of complex motor behaviour.
Prenatal exposure to polybrominated diphenylether 99 enhances the function of the glutamate–nitric oxide–cGMP pathway in brain in vivo and in cultured neurons
Authors: Llansola Marta , Erceg Slaven , Monfort Pilar , Montoliu Carmina , Felipo Vicente 
Published: January 2007

AbstractPolybrominated diphenylethers (PBDEs) are widely used as flame retardants. Significant amounts of PBDEs are present in the milk of lactating women. The possible neurotoxic effects of PBDEs are not well known. Perinatal exposure to PBDEs affects both motor and cognitive functions by mechanisms that remain unclear. Some types of learning depend on N‐methyl‐d‐aspartate receptor activation, which increases intracellular calcium that binds to calmodulin and activates nitric oxide synthase, increasing nitric oxide formation that activates guanylate cyclase, increasing cGMP formation. Part of this cGMP is released to the extracellular fluid. We studied whether prenatal exposure of rats to PBDE99 alters the function of this glutamate–nitric oxide–cGMP pathway in rat brain in vivo. At 10 weeks of age, rats treated with PBDE99 showed increased function of the glutamate–nitric oxide–cGMP pathway in brain in vivo, as assessed by microdialysis in freely moving rats. The increased function of the pathway was reproduced in primary cultures of cerebellar neurons prepared from rats prenatally exposed to PBDE99 as well as in neurons cultured from normal rats and treated in vitro with PBDE99. Increased calmodulin content and activation of soluble guanylate cyclase by nitric oxide contributed to the increased function of the pathway.
Early functional development of interneurons in the zebrafish olfactory bulb
Authors: Mack‐Bucher Julia A. , Li Jun , Friedrich Rainer W. 
Published: January 2007

AbstractIn the adult olfactory bulb (OB) of vertebrates, local GABAergic interneurons (INs) mediate recurrent and lateral inhibition between the principal neurons of the OB, the mitral cells (MCs), and play pivotal roles in the processing of odor‐evoked activity patterns. The properties and functions of INs in the developing OB are, however, not well understood. We studied the functional development of INs in the OB of living zebrafish larvae 3–6 days postfertilization using anatomical techniques and in‐vivo two‐photon Ca2+ imaging. We identified MCs and INs by cell‐type‐specific expression of transgenic fluorescent markers and found that the IN : MC ratio was lower than in the adult fish. Moreover, the fraction of INs responding with Ca2+ signals to a set of natural odors was substantially lower than in adults. Odors of different chemical classes evoked overlapping patterns of Ca2+ signals that were concentrated in the center of the IN layer. The GABAA receptor agonists GABA and muscimol strongly suppressed odor responses, whereas a GABAA receptor antagonist enhanced responses and altered the spatial distribution of odor‐evoked activity. These results indicate that IN odor responses at early developmental stages are sparse and exhibit no obvious chemotopic organization. Nevertheless, GABAergic signaling is already inhibitory at early stages of OB development and strongly influences odor‐evoked activity patterns. Hence, INs already participate in the processing of odor information at very early stages of OB development even though the majority of INs emerge only at later stages.
Melatonin induces gene‐specific effects on rhythmic mRNA expression in the pars tuberalis of the Siberian hamster (Phodopus sungorus)
Authors: Wagner Gabriela C. , Johnston Jonathan D. , Tournier Benjamin B. , Ebling Francis J. P. , Hazlerigg David G. 
Published: January 2007

AbstractIn mammals, circadian and photoperiodic information is encoded in the pineal melatonin signal. The pars tuberalis (PT) of the pituitary is a melatonin target tissue, which transduces photoperiodic changes and drives seasonal changes in prolactin secretion from distal lactotroph cells. Measurement of photoperiodic time in the PT is believed to occur through melatonin dependent changes in clock gene expression, although it is unclear whether the PT should be considered a melatonin sensitive peripheral oscillator. We tested this hypothesis in the Siberian hamster (Phodopus sungorus) firstly by investigating the effects of melatonin injection, and secondly by determining whether temporal variation in gene expression within the PT persists in the absence of a rhythmic melatonin signal. Hamsters preconditioned to long days were treated with melatonin during the late light phase, to advance the timing of the nocturnal melatonin peak, or placed in constant light for one 24 h cycle, thereby suppressing endogenous melatonin secretion. Gene expression in the PT was measured by in situ hybridization. We show that melatonin rapidly induces cry1 mRNA expression without the need for a prolonged melatonin‐free interval, acutely inhibits mt1 expression, advances the timing of peak rev‐erbα expression and modulates per1 expression. With the exception of cry1, these genes continue to show temporal changes in expression over a first cycle in the absence of a melatonin signal. Our data are consistent with the hypothesis that the hamster PT contains a damped endogenous circadian oscillator, which requires a rhythmic melatonin signal for long‐term synchronization.
Developmental divergence of sleep‐wake patterns in orexin knockout and wild‐type mice
Authors: Blumberg Mark S. , Coleman Cassandra M. , Johnson Eric D. , Shaw Cynthia 
Published: January 2007

AbstractNarcolepsy, a disorder characterized by fragmented bouts of sleep and wakefulness during the day and night as well as cataplexy, has been linked in humans and nonhuman animals to the functional integrity of the orexinergic system. Adult orexin knockout mice and dogs with a mutation of the orexin receptor exhibit symptoms that mirror those seen in narcoleptic humans. As with narcolepsy, infant sleep‐wake cycles in humans and rats are highly fragmented, with consolidated bouts of sleep and wakefulness developing gradually. Based on these common features of narcoleptics and infants, we hypothesized that the development of sleep‐wake fragmentation in orexin knockout mice would be expressed as a developmental divergence between knockouts and wild‐types, with the knockouts lagging behind the wild‐types. We tested this hypothesis by recording the sleep‐wake patterns of infant orexin knockout and wild‐type mice across the first three postnatal weeks. Both knockouts and wild‐types exhibited age‐dependent, and therefore orexin‐independent, quantitative and qualitative changes in sleep‐wake patterning. At 3 weeks of age, however, by which time the sleep and wake bouts of the wild‐types had consolidated further, the knockouts lagged behind the wild‐types and exhibited significantly more bout fragmentation. These findings suggest the possibility that the fragmentation of behavioural states that characterizes narcolepsy in adults reflects reversion back toward the more fragmented sleep‐wake patterns that characterize infancy.
Prokineticin 2 depolarizes paraventricular nucleus magnocellular and parvocellular neurons
Authors: Yuill Erik A. , Hoyda Ted D. , Ferri Catharine C. , Zhou Qun‐Yong , Ferguson Alastair V. 
Published: January 2007

AbstractBlind whole‐cell patch‐clamp techniques were used to examine the effects of prokineticin 2 (PK2) on the excitability of magnocellular (MNC), parvocellular preautonomic (PA), and parvocellular neuroendocrine (NE) neurons within the hypothalamic paraventricular nucleus (PVN) of the rat. The majority of MNC neurons (76%) depolarized in response to 10 nm PK2, effects that were eliminated in the presence of tetrodotoxin (TTX). PK2 also caused an increase in excitatory postsynaptic potential (EPSP) frequency, a finding that was confirmed by voltage clamp recordings demonstrating increases in excitatory postsynaptic current (EPSC) frequency. The depolarizing effects of PK2 on MNC neurons were also abolished by kynurenic acid (KA), supporting the conclusion that the effects of PK2 are mediated by the activation of glutamate interneurons within the hypothalamic slice. PA (68%) and NE (67%) parvocellular neurons also depolarized in response to 10 nm PK2. However, in contrast to MNC neurons, these effects were maintained in TTX, indicating that PK2 directly affects PA and NE neurons. PK2‐induced depolarizations observed in PA and NE neurons were found to be concentration‐related and receptor mediated, as experiments performed in the presence of A1MPK1 (a PK2 receptor antagonist) abolished the effects of PK2 on these subpopulations of neurons. The depolarizing effects of PK2 on PA and NE neurons were also shown to be abolished by PD 98059 (a mitogen activated protein kinase (MAPK) inhibitor) suggesting that PK2 depolarizes PVN parvocellular neurons through a MAPK signalling mechanism. In combination, these studies have identified separate cellular mechanisms through which PK2 influences the excitability of different subpopulations of PVN neurons.
Inactivation of the prelimbic, but not infralimbic, prefrontal cortex impairs the contextual control of response conflict in rats
Authors: Marquis Jean‐Philippe , Killcross Simon , Haddon Josephine E. 
Published: January 2007

AbstractOne fundamental function of the prefrontal cortex (PFC) is to guide context‐appropriate behaviour in situations of response conflict. Haddon and Killcross recently developed a task in rats which mimics some aspects of response conflict seen in human cognitive paradigms such as the Stroop task. Using this paradigm they demonstrated that large PFC lesions including the prelimbic (PL), infralimbic (IL) and anterior cingulate cortices (ACC) selectively impaired performance on incongruent trials which required the use of task‐setting contextual cues to control responding in the face of ambiguous response information. The current experiment was conducted to determine whether specific PFC regions were responsible for the deficit in incongruent performance. Rats were trained on two instrumental biconditional discriminations, one auditory and one visual, in two different contexts. Following acquisition, rats were implanted with guide cannulae aimed at the PL or the IL cortices of the rat prefrontal cortex. Following retraining, rats received microinfusions of the GABAA agonist muscimol or artificial cerebrospinal fluid (aCSF) into either the PL or the IL prior to presentations of novel congruent and incongruent audiovisual compounds of the training stimuli in extinction. Results showed that temporary inactivation of the PL cortex led to a selective deficit on incongruent compound trials, but left congruent, and hence biconditional task performance intact. By contrast, IL inactivation had no effect on the accuracy of responding during either congruent or incongruent trials. These results suggest that the PL cortex is necessary for the use of task‐setting contextual cues to control responding to conflicting information.
Enhanced synaptic excitation–inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsy
Authors: Stief F. , Zuschratter W. , Hartmann K. , Schmitz D. , Draguhn A. 
Published: January 2007

AbstractA common feature of all epileptic syndromes is the repetitive occurrence of pathological patterns of synchronous neuronal activity, usually combined with increased neuronal discharge rates. Inhibitory interneurons of the hippocampal formation control both neuronal synchronization as well as the global level of activity and are therefore of crucial importance for epilepsy. Recent evidence suggests that changes in synaptic inhibition during temporal lobe epilepsy are rather specific, resulting from selective death or alteration of interneurons in specific hippocampal layers. Hence, epilepsy‐induced changes have to be analysed separately for different types of interneurons. Here, we focused on GABAergic neurons located at the border between stratum radiatum and stratum lacunosum‐moleculare of hippocampal area CA1 (SRL interneurons), which are included in feedforward inhibitory circuits. In chronically epileptic rats at 6–8 months after pilocarpine‐induced status epilepticus, frequencies of spontaneous and miniature inhibitory postsynaptic currents were reduced, yielding an almost three‐fold increase in excitation–inhibition ratio. Consistently, action potential frequency of SRL interneurons was about two‐fold enhanced. Morphological alterations of the interneurons indicate that these functional changes were accompanied by remodelling of the local network, probably resulting in a loss of functional inhibitory synapses without conceivable cell death. Our data indicate a strong increase in activity of interneurons in dendritic layers of the chronically epileptic CA1 region. This alteration may enhance feedforward inhibition and rhythmogenesis and – together with specific changes in other interneurons – contribute to seizure susceptibility and pathological synchronization.
Intermittent ethanol exposure induces inflammatory brain damage and causes long‐term behavioural alterations in adolescent rats
Authors: Pascual Maria , Blanco Ana M. , Cauli Omar , Miñarro Jose , Guerri Consuelo 
Published: January 2007

AbstractAdolescent brain development seems to be important for the maturation of brain structures and behaviour. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage. Because we have demonstrated that chronic ethanol treatment induces inflammatory processes in the brain, we investigate whether intermittent ethanol intoxication enhances cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) in adolescent rats, and whether these mediators induce brain damage and cause permanent cognitive dysfunctions. Adolescent rats were exposed to ethanol (3.0 g/kg) for two consecutive days at 48‐h intervals over 14 days. Levels of COX‐2, iNOS and cell death were assessed in the neocortex, hippocampus and cerebellum 24 h after the final ethanol administration. The following day or 20 days after the final injection (adult stage), animals were tested for different behavioural tests (conditional discrimination learning, rotarod, object recognition, beam‐walking performance) to assess cognitive and motor functions. Our results show that intermittent ethanol intoxication upregulates COX‐2 and iNOS levels, and increases cell death in the neocortex, hippocampus and cerebellum. Furthermore, animals treated with ethanol during adolescence exhibited behavioural deficits that were evident at the end of ethanol treatments and at the adult stage. Administration of indomethacin, a COX‐2 inhibitor, abolishes the induction of COX‐2 and iNOS expression and cell death, preventing ethanol‐induced behavioural deficits. These findings indicate that binge pattern exposure to ethanol during adolescence induces brain damage by inflammatory processes and causes long‐lasting neurobehavioural consequences. Accordingly, administering indomethacin protects against ethanol‐induced brain damage and prevents detrimental ethanol effects on cognitive and motor processes.
ω‐Conotoxin CVIB differentially inhibits native and recombinant N‐ and P/Q‐type calcium channels
Authors: Motin Leonid , Yasuda Takahiro , Schroeder Christina I. , Lewis Richard J. , Adams David J. 
Published: January 2007

Abstractω‐Conotoxins are routinely used as selective inhibitors of different classes of voltage‐gated calcium channels (VGCCs) in excitable cells. In the present study, we examined the potent N‐type VGCC antagonist ω‐conotoxin CVID and non‐selective N‐ and P/Q‐type antagonist CVIB for their ability to block native VGCCs in rat dorsal root ganglion (DRG) neurons and recombinant VGCCs expressed in Xenopus oocytes. ω‐Conotoxins CVID and CVIB inhibited depolarization‐activated whole‐cell VGCC currents in DRG neurons with pIC50 values of 8.12 ± 0.05 and 7.64 ± 0.08, respectively. Inhibition of Ba2+ currents in DRG neurons by CVID (∼ 66% of total) appeared to be irreversible for > 30 min washout, whereas Ba2+ currents exhibited rapid recovery from block by CVIB (≥ 80% within 3 min). The recoverable component of the Ba2+ current inhibited by CVIB was mediated by the N‐type VGCC, whereas the irreversibly blocked current (∼ 22% of total) was attributable to P/Q‐type VGCCs. ω‐Conotoxin CVIB reversibly inhibited Ba2+ currents mediated by N‐ (CaV2.2) and P/Q‐ (CaV2.1), but not R‐ (CaV2.3) type VGCCs expressed in Xenopus oocytes. The α2δ1 auxiliary subunit co‐expressed with CaV2.2 and CaV2.1 reduced the sensitivity of VGCCs to CVIB but had no effect on reversibility of block. Determination of the NMR structure of CVIB identified structural differences to CVID that may underlie differences in selectivity of these closely related conotoxins. ω‐Conotoxins CVIB and CVID may be useful as antagonists of N‐ and P/Q‐type VGCCs, particularly in sensory neurons involved in processing primary nociceptive information.
JNK1 contributes to metabotropic glutamate receptor‐dependent long‐term depression and short‐term synaptic plasticity in the mice area hippocampal CA1
Authors: Li Xin‐Mei , Li Chen‐Chen , Yu Shan‐Shan , Chen Ju‐Tao , Sabapathy Kanaga , Ruan Di‐Yun 
Published: January 2007

AbstractSeveral recent reports implicate an important role played by c‐Jun N‐terminal kinases (JNKs) in long‐term potentiation (LTP). However, little is known about how the isoforms of JNKs participate in synaptic plasticity. Here we showed that short‐term synaptic plasticity was impaired in the hippocampal area CA1 of JNK1‐deficient (JNK1–/–) mice; these mice showed normal LTP in response to a strong tetanus and no alteration of N‐methyl‐d‐aspartate receptor‐dependent long‐term depression (LTD) in the hippocampus. However, LTD induced either by group I metabotropic glutamate receptors (mGluRs) agonist dihydroxyphenylglycine or by paired‐pulse low‐frequency stimulation was absent in both the JNK1–/– slices and in JNK inhibitor anthrax [1, 9‐cd] pyrazol‐6(2H)‐1 (SP600125)‐pretreated slices. Induction of mGluR‐dependent LTD resulted in an increase in phosphorylation of JNK1 substrates, including p‐c‐Jun and p‐ATF2 in wild‐type (WT) mice, and these increases failed to occur in the JNK1–/– or SP600125‐pretreated mice. These results demonstrated that JNK1 played a crucial role in the short‐term synaptic plasticity and mGluR‐dependent LTD, whereas hippocampus LTP was not affected by JNK1 deficiency.