bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurogenesis, learning and associative strength
Authors: Waddell Jaylyn , Shors Tracey J. 
Published: June 2008

AbstractThough the role of the hippocampus in processes of learning and memory is well established, the role of new neurons generated there is less understood. Training on some associative learning tasks increases the likelihood that new cells in the subgranular zone of the dentate gyrus will survive. In the rat, an effective training procedure is trace eyeblink conditioning, in which a conditioned stimulus (CS) is paired with an aversive stimulation to the eyelid (unconditioned stimulus; US), but the stimuli are separated by a temporal gap. Here, we manipulated the asymptote or rate of acquisition during trace conditioning, and examined survival of cells generated 1 week before training. Acquisition was disrupted by decreasing associative strength by insertion of unpredicted USs or slowed with latent inhibition. The number of cells was increased in animals that were trained with trace conditioning, irrespective of the decrease in associative strength or slowed acquisition. Disrupting acquisition with unsignaled USs still increased cell numbers, suggesting that the learning effect on cell survival is not dependent on reliable expression of the conditioned response. Further, animals in the latent inhibition conditions that learned but required more trials also retained more of the new cells than animals requiring fewer trials. The number of cells that survived after the effective training procedures was similar to the number of cells that were available for rescue at the beginning of training. Thus, learning can rescue the majority of cells expressed at the beginning of training, and does so most effectively when acquisition requires many trials.
Prenatal nicotine exposure changes natural and drug‐induced reinforcement in adolescent male rats
Authors: Franke Ryan M. , Park Minjung , Belluzzi James D. , Leslie Frances M. 
Published: June 2008

AbstractClinical studies have demonstrated an increased incidence of substance misuse and obesity in adolescents whose mothers smoked during pregnancy. Although dopamine systems that mediate natural and drug‐induced reinforcement have been shown in animal studies to be altered by gestational nicotine treatment, it is not clear whether there are concomitant changes in reinforcement sensitivity. To test whether prenatal nicotine exposure influences sensitivity to natural and drug rewards, timed pregnant rats were implanted with osmotic minipumps delivering saline or nicotine (3 mg/kg/day) from gestational day 4 to 18. Male offspring were tested as adolescents, on postnatal day 32, for operant responding maintained by sucrose pellets or i.v. cocaine (200 or 500 μg/kg per injection). Cocaine‐induced stereotypy andc‐fosmRNA expression in cortex and striatum were also examined. Complex changes in reward circuitry were observed in the offspring of nicotine‐exposed dams. Nicotine‐exposed adolescents did not self‐administer the low dose of cocaine, but, at the higher dose, exhibited significantly greater cocaine intake andc‐fosmRNA expression in nucleus accumbens than did controls. In contrast, control animals showed significantly greater drug‐induced stereotypy at both cocaine doses. Operant responding maintained by sucrose was also influenced by gestational nicotine exposure. At a fixed ratio (FR) 1 schedule, although the number of pellets eaten by the two experimental groups was equivalent, more pellets were left uneaten by nicotine‐exposed offspring. At FR2 and FR5 schedules, the responding maintained by sucrose pellets was lower in nicotine‐exposed offspring. These findings suggest that nicotine exposure during gestation may induce changes in both natural and drug reward pathways.
Juvenile methylphenidate modulates reward‐related behaviors and cerebral blood flow by decreasing cortical D3 receptors
Authors: Andersen Susan L. , Napierata Lee , Brenhouse Heather C. , Sonntag Kai C. 
Published: June 2008

AbstractAttention deficit hyperactivity disorder is associated with reduced cortical blood flow that is reversible with exposure to the psychostimulant methylphenidate (MPH). D3 dopamine receptors modulate stimulant‐induced changes in blood flow and are associated with reward processing during young adulthood, but their role in the enduring effects of MPH during development is unknown. Rats were given vehicle (VEH) or MPH (2 mg/kg between postnatal days 20–35) and assessed in young adulthood for regional cerebral blood volume (rCBV) after MPH challenge and mRNA expression levels of dopamine receptors. To probe D3 receptor involvement, juvenile subjects were exposed to VEH, MPH, the D3‐preferring agonist ±7‐OHDPAT (0.3 mg/kg), the D3 antagonist nafadotride (Naf; 0.05, 0.5 or 5.0 mg/kg) or a Naf (0.05 mg/kg)/MPH combination, and assessed biochemically and behaviorally. Juvenile MPH exposure increased MPH‐induced rCBV in the cingulate and medial prefrontal cortex and thalamus in adulthood. Behaviorally, juvenile MPH‐ or ±7‐OHDPAT‐exposed subjects demonstrated an aversion to cocaine‐associated environments, which was prevented by juvenile co‐treatment with MPH and Naf, or with adult cortical microinjections of ±7‐OHDPAT. Cortical D3 mRNA levels significantly decreased by 23.8 ± 6.7% in MPH‐treated subjects and normalized with combined Naf/MPH treatment, with no change in the other dopamine receptors. Enhanced cortical responsiveness to psychostimulants may occur through a reduction in D3 receptors, which in turn reduces drug‐seeking behavior. These data provide evidence for a postnatal sensitive period when juvenile MPH exposure is able to alter cortical development.
Protein degradation, as with protein synthesis, is required during not only long‐term spatial memory consolidation but also reconsolidation
Authors: Artinian Julien , McGauran Anne‐Marie T. , De Jaeger Xavier , Mouledous Lionel , Frances Bernard , Roullet Pascal 
Published: June 2008

AbstractThe formation of long‐term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin‐proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis‐dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation.
Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation
Authors: Patel Sachin , Hillard Cecilia J. 
Published: June 2008

AbstractDaily life stressors are a major environmental factor contributing to precipitation and exacerbation of mental illness. Animal models using repeated homotypic stress induce anxious and depressive phenotypes and are used to study the pathophysiology of affective disorders. Here we discuss data demonstrating that repeated homotypic stress produces temporally and anatomically distinct changes in endocannabinoid signaling components within stress‐responsive brain regions. We also present evidence describing the neural and behavioral correlates of these adaptations in endocannabinoid signaling. These data support a role for endocannabinoid signaling in the central nervous system response to chronic, homotypic stress, and specifically in the process of stress–response habituation. The clinical implications of these findings for the pathophysiology and treatment of affective disorders are discussed.
Mu‐opioid receptor activation induces transcriptional plasticity in the central extended amygdala
Authors: Befort K. , Filliol D. , Ghate A. , Darcq E. , Matifas A. , Muller J. , Lardenois A. , Thibault C. , Dembele D. , Le Merrer J. , Becker J. A. J. , Poch O. , Kieffer B. L. 
Published: June 2008

AbstractAddiction develops from the gradual adaptation of the brain to chronic drug exposure, and involves genetic reprogramming of neuronal function. The central extended amygdala (EAc) is a network formed by the central amygdala and the bed nucleus of the stria terminalis. This key site controls drug craving and seeking behaviors, and has not been investigated at the gene regulation level. We used Affymetrix microarrays to analyze transcriptional activity in the murine EAc, with a focus on mu‐opioid receptor‐associated events because these receptors mediate drug reward and dependence. We identified 132 genes whose expression is regulated by a chronic escalating morphine regimen in the EAc from wild‐type but not mu‐opioid receptor knockout mice. These modifications are mostly EAc‐specific. Gene ontology analysis reveals an overrepresentation of neurogenesis, cell growth and signaling protein categories. A separate quantitative PCR analysis of genes in the last of these groups confirms the dysregulation of both orphan (Gpr88) and known (DrD1A,Adora2A,Cnr1,Grm5,Gpr6) G protein‐coupled receptors, scaffolding (PSD95,Homer1) and signaling (Sgk,Cap1) proteins, and neuropeptides (CCK,galanin). These transcriptional modifications do not occur following a single morphine injection, and hence result from long‐term adaptation to excessive mu receptor activation. Proteins encoded by these genes are classically associated with spine modules function in other brain areas, and therefore our data suggest a remodeling of EAc circuits at sites where glutamatergic and monoaminergic afferences interact. Together, mu receptor‐dependent genes identified in this study potentially contribute to drug‐induced neural plasticity, and provide a unique molecular repertoire towards understanding drug craving and relapse.
GABAergic mechanism mediated via D1receptors in the rat periaqueductal gray participates in the micturition reflex: anin vivomicrodialysis study
Authors: Kitta Takeya , Matsumoto Machiko , Tanaka Hiroshi , Mitsui Takahiko , Yoshioka Mitsuhiro , Nonomura Katsuya 
Published: June 2008

AbstractThe periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and γ‐aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation usingin vivomicrodialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D1receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D1receptor blockade. The D1receptor antagonist prevented micturition‐induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D2receptor antagonist nor a D1/D2receptor agonist affected these neurochemical and physiological parameters. Micturition‐induced inhibition of GABA was not observed in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats, an animal model of Parkinson’s disease. 6‐OHDA‐lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D1receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D1receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6‐OHDA‐lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson’s disease.
Synaptogenesis in the mouse olfactory bulb during glomerulus development
Authors: Blanchart Albert , Romaguera Miriam , García‐Verdugo Jose M. , De Carlos Juan A. , López‐Mascaraque Laura 
Published: June 2008

AbstractSynaptogenesis is essential for the development of neuronal networks in the brain. In the olfactory bulb (OB) glomeruli, numerous synapses must form between sensory olfactory neurons and the dendrites of mitral/tufted and periglomerular cells. Glomeruli develop from E13 to E16 in the mouse, coincident with an increment of the neuropil in the border between the external plexiform (EPL) and olfactory nerve layers (ONL), coupled to an extensive labelling of phalloidin and GAP‐43 from the ONL to EPL. We have tracked synaptogenesis in the OB during this period by electron microscopy (EM) and immunolabelling of the transmembrane synaptic vesicle glycoprotein SV‐2. No SV‐2 labelling or synapses were detected at E13, although electrodense junctions lacking synaptic vesicles could be observed by EM. At E14, sparse SV‐2 labelling appears in the most ventral and medial part of the incipient OB, which displays a ventro‐dorsal gradient by E15 but covers the entire OB by E16. These data establish a spatio‐temporal pattern of synaptogenesis, which perfectly matches with the glomeruli formation in developing OB.
Individual differences in disgust sensitivity modulate neural responses to aversive/disgusting stimuli
Authors: Mataix‐Cols David , An Suk Kyoon , Lawrence Natalia S. , Caseras Xavier , Speckens Anne , Giampietro Vincent , Brammer Michael J. , Phillips Mary L. 
Published: June 2008

AbstractLittle is known about how individual differences in trait disgust sensitivity modulate the neural responses to disgusting stimuli in the brain. Thirty‐seven adult healthy volunteers completed the Disgust Scale (DS) and viewed alternating blocks of disgusting and neutral pictures from the International Affective Picture System while undergoing fMRI scanning. DS scores correlated positively with activations in brain regions previously associated with disgust (anterior insula, ventrolateral prefrontal cortex–temporal pole, putamen–globus pallidus, dorsal anterior cingulate, and visual cortex) and negatively with brain regions involved in the regulation of emotions (dorsolateral and rostral prefrontal cortices). The results were not confounded by biological sex, anxiety or depression scores, which were statistically controlled for. Disgust sensitivity, a behavioral trait that is normally distributed in the general population, predicts the magnitude of the individual’s neural responses to a broad range of disgusting stimuli. The results have implications for disgust‐related psychiatric disorders.
Progression of benign prostatic hyperplasia: systematic review of the placebo arms of clinical trials
Authors: Emberton Mark , Fitzpatrick John M. , Garcia‐Losa Manuel , Qizilbash Nawab , Djavan Bob 
Published: June 2008

OBJECTIVETo systematically review the placebo arms of randomized trials of medical therapy for benign prostatic hyperplasia (BPH) and thus estimate rates of progression.METHODSWe searched PubMed, the Cochrane Trials Register and the USA Food and Drug Administration website. Retrieved citations were reviewed in two stages: a title and abstract screen, followed by a review of selected full‐length articles. The inclusion criterion for studies were trials of BPH with >100 patients in the placebo group.RESULTSFrom 1774 citations screened, 16 eligible studies were found with a total of 12 158 patients. The range of mean baseline age was 62.6–66.5 years, for prostate volume 33.9–61.0 mL and for maximum urinary flow 8.6–11.6 mL/s. With studies spanning 12–48 months, the rates of surgery were 1–10% and for acute urinary retention 0.4–6.6%. Most studies showed progression, based on a worsening in clinical outcomes of the change from baseline in prostate volume and maximum urinary flow. Statistical heterogeneity prevented a quantitative synthesis of the data.CONCLUSIONThis systematic review confirms BPH disease progression in the form of increased prostate volume, reduction in maximum urinary flow rate and an increase in the risk of acute urinary retention and surgery. To provide quantitative estimates of effect, access to data from individual participants would be required.
Antitumour effect of electrochemotherapy with bleomycin on human prostate cancer xenograft
Authors: Ueki Tei‐ichiro , Uemura Hiroji , Nagashima Yoji , Ohta Shinsuke , Ishiguro Hitoshi , Kubota Yoshinobu 
Published: June 2008

OBJECTIVETo investigate the antitumour effect of electroporation (EP), a drug delivery system that has been shown to be effective synergistically with antitumour drugs, with bleomycin on the growth of prostate cancer xenografts in nude mice.MATERIALS AND METHODSPC‐3 cells were implanted subcutaneously into nude mice. After determination of the optimal conditions of electric pulse voltage and bleomycin dose, tumour growth in mice treated with EP plus bleomycin was compared with that in mice receiving EP alone, bleomycin alone or no treatment. In all four groups, apoptosis in the tumours was assessed.RESULTSThere was a significant reduction in tumour growth in mice that received EP with bleomycin. Apoptotic cells in tumours at 24 h after treatment with EP plus bleomycin showed a significant difference compared with the other three groups, but not at 12 h after treatment.CONCLUSIONSThese results indicate the possibility that EP with bleomycin could be effective as an ablation therapy for prostate cancer, especially androgen‐independent cancer.
M129V polymorphism in the prion protein gene is not associated with mesial temporal lobe epilepsy in a Han Chinese population
Authors: Wang X. , Sun W. , Zhu X. , Wu X. , Li L. , Zhu S. , Du T. , Liu Y. , Niu N. , Wang Y. , Liu Y. 
Published: June 2008

Background and purpose:  Prion protein (PrP) predominantly localized at synapses can modulate neuronal excitability. The prion protein gene (PRNP) has been considered one of the candidate genes that play a role in seizure susceptibility. A recent study demonstrated that the 129V allele in the PRNP gene was associated with susceptibility to temporal lobe epilepsy (TLE) in female patients in an Italian population. We screened variations in the open‐reading frame (ORF) of the PRNP gene and also replicated the association of the M129V polymorphism with TLE in a Han Chinese population.Methods:  The M129V polymorphism was genotyped in 320 MTLE patients and 558 non‐epilepsy controls. All subjects were Han Chinese.Results:  No novel polymorphism in the ORF of the PRNP gene was detected. Differences in the genotype distributions and allele frequencies of this polymorphism between cases and controls were insignificant (P = 0.24). Further analysis with stratification of the results by gender or age and analysis of clinical features in relation to M129V genotypes also yielded negative findings.Conclusions:  The present study provides evidence that the M129V polymorphism in the PRNP gene is not associated with MTLE in a Han Chinese population.
Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series
Authors: Nebuchennykh M. , Løseth S. , Jorde R. , Mellgren S. I. 
Published: June 2008

Background and purpose:  North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy.Methods:  Seventy patients with symptoms and signs of sensory polyneuropathy were included. Cases with known causes of neuropathy were excluded. All patients underwent a 2 h oral glucose tolerance test (OGTT). Nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsy with assessment of intra‐epidermal nerve fibre (IENF) density were performed.Results:  Sixteen patients (23%) had impaired glucose metabolism (IGM): 2 (3%) were found to have diabetes, 9 (13%) had IGT, 3 (4%) had impaired fasting glucose (IFG) and 2 (3%) both IFG and IGT. About 62% of the patients with IGM and polyneuropathy and 50% of those with chronic idiopathic axonal polyneuropathy (CIAP) had abnormalities on NCS. Reduction of IENF occurred in 37% of the patients with IGM and 43% of those with CIAP.Conclusions:  Patients with polyneuropathy and IGM had essentially the same degree of involvement of small and large nerve fibres as patients with CIAP. IGT seems less frequent in Norwegian patients with polyneuropathy than reported in North American populations.
Enhanced CREB and DARPP‐32 phosphorylation in the nucleus accumbens and CREB, ERK, and GluR1 phosphorylation in the dorsal hippocampus is associated with cocaine‐conditioned place preference behavior
Authors: Tropea Thomas F. , Kosofsky Barry E. , Rajadhyaksha Anjali M. 
Published: June 2008

AbstractEnvironment‐induced relapse is a major concern in drug addiction because of the strong associations formed between drug reward and environment. Cocaine‐conditioned place preference is an ideal experimental tool to examine adaptations in the molecular pathways that are activated upon re‐exposure to an environment previously paired with drug reward. To better understand the mechanism of cocaine‐conditioned place preference we have used western blot analysis to examine changes in phosphorylation of cAMP‐response element binding protein (CREB), dopamine‐ and cyclic AMP‐regulated phosphoprotein 32 (DARPP‐32), extracellular signal‐regulated kinase (ERK) and GluR1, key molecular substrates altered by cocaine, in the nucleus accumbens (NAc) and dorsal hippocampus (DHC) of C57BL/6 mice. Our studies revealed that re‐exposing mice to an environment in which they were previously given cocaine resulted in increased levels of Ser133 phospho‐CREB and Thr34 phospho‐DARPP‐32 with a corresponding decrease in Thr75 phospho‐DARPP‐32 in the NAc. In DHC there were increased levels of phospho‐CREB, Thr183/Tyr185 phospho‐ERK, and Ser845 phospho‐GluR1. These data suggest that the formation of contextual drug reward associations involves recruitment of the DHC‐NAc circuit with activation of the DARPP‐32/CREB pathway in the NAc and the ERK/CREB pathway in the DHC.