bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐inhibitory interactions between GABAAand P2X channels in myenteric neurones
Authors: Karanjia Rustum , García‐Hernández Luz M. , Miranda‐Morales Marcela , Somani Nureen , Espinosa‐Luna Rosa , Montaño Luis M. , Barajas‐López Carlos 
Published: June 2006

AbstractInhibitory interactions between GABAA[induced by γ‐aminobutyric acid (GABA)] and P2X [activated by adenosine 5′‐triphosphate (ATP)] receptors of myenteric neurones from the guinea pig small intestine were characterized using whole‐cell recordings. Currents induced by GABA (IGABA) or ATP (IATP) were inhibited by picrotoxin or pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid, respectively. Currents induced by GABA + ATP (IGABA+ATP) were only as large as the current induced by the most effective transmitter, revealing current occlusion. This occlusion requires maximal activation of at least one of these receptors. Sequential applications of neurotransmitters, and kinetic and pharmacological properties of IGABA+ATPindicate that they are carried through both GABAAand P2X channels. ATP did not affect IGABAin neurones: (i) in which P2X channels were not present; (ii) after inhibiting P2X channels with Ca2+(iii) in the presence of pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid, a P2X receptor antagonist; (iv) after P2X receptor desensitization or (v) at IATPreversal potential. Similarly, GABA did not affect P2X‐mediated currents in neurones: (i) in which GABAAchannels were not present; (ii) in the presence of picrotoxin, a GABAAchannel blocker; (iii) after GABAAreceptor desensitization or (iv) at the IGABAreversal potential. Current occlusion occurred as fast as current activation and it was still present in the absence of Ca2+, at 11 °C, after adding to the pipette solution a cocktail of protein kinase inhibitors (staurosporine + genistein + K‐252a), after substituting the GTP in the pipette with GDP‐β‐S and after treating the cells withN‐ethylmaleimide. Taken together, all of these results are consistent with a model of cross‐inhibition between GABAAand P2X.
Differential expression of GABAA and glycine receptors in ALS‐resistant vs. ALS‐vulnerable motoneurons: possible implications for selective vulnerability of motoneurons
Authors: Lorenzo Louis‐Etienne , Barbe Annick , Portalier Paule , Fritschy Jean‐Marc , Bras Hélène 
Published: June 2006

SummaryAmyotrophic lateral sclerosis (ALS) is a devastating motoneuronal degenerative disease, which is inevitably fatal in adults. ALS is characterized by an extensive loss of motoneurons in the cerebrospinal axis, except for those motoneurons that control eye movements and bladder contraction. The reason for this selectivity is not known. Systematic differences have been found in the organization of excitatory synaptic transmission in ALS‐resistant vs. ALS‐susceptible motor nuclei. However, although motoneurons express high levels of glycine receptors (GlyR) and GABAA receptors (GABAAR), no such studies have been carried out yet for inhibitory synaptic transmission. In this study, we compared the subunit composition, patterns of expression, density and synaptic localization of inhibitory synaptic receptors in ALS‐resistant (oculomotor, trochlear and abducens) and ALS‐vulnerable motoneurons (trigeminal, facial and hypoglossi). Triple immunofluorescent stainings of the major GABAAR subunits (α1, α2, α3, and α5), the GlyR α1 subunit and gephyrin, were visualized by confocal microscopy and analysed quantitatively. A strong correlation was observed between the vulnerability of motoneurons and the subunit composition of GABAAR, the GlyR/GABAAR density ratios and the incidence of synaptic vs. extrasynaptic GABAAR. These differences contrast strikingly with the uniform gephyrin cluster density and synaptic GlyR levels recorded in all motor nuclei examined. These results suggest that the specific patterns of inhibitory receptor organization observed might reflect functional differences that are relevant to the physiopathology of ALS.
Huntingtin inclusions do not down‐regulate specific genes in the R6/2 Huntington's disease mouse
Authors: Sadri‐Vakili G. , Menon A. S. , Farrell L. A. , Keller‐McGandy C. E. , Cantuti‐Castelvetri I. , Standaert D. G. , Augood S. J. , Yohrling G. J. , Cha J.‐H. J. 
Published: June 2006

AbstractTranscriptional dysregulation is a central pathogenic mechanism in Huntington's disease (HD); HD and transgenic mouse models of HD demonstrate down‐regulation of specific genes at the level of mRNA expression. Furthermore, neuronal intranuclear inclusions (NIIs) have been identified in the brains of R6/2 mice and HD patients. One possibility is that NIIs contribute to transcriptional dysregulation by sequestering transcription factors. We therefore assessed the relationship between NIIs and transcriptional dysregulation in the R6/2 mouse, using double‐label in situ hybridization combined with immunohistochemistry, and laser capture microdissection combined with quantitative real‐time PCR. There was no difference in transcript levels of specific genes between NII‐positive and NII‐negative neurons. These results demonstrate that NIIs do not cause decreases in D2, PPE and PSS mRNA levels in R6/2 striatum and therefore are not involved in the down‐regulation of these specific genes in this HD model. In addition, these observations argue against the notion that NIIs protect against transcriptional dysregulation in HD.
Cardiovascular and respiratory responses to a panicogenic agent in anaesthetised female Wistar rats at different stages of the oestrous cycle
Authors: Brack K. E. , Jeffery S. M. T. , Lovick T. A. 
Published: June 2006

AbstractIn urethane‐anaesthetised female Wistar rats, intravenous injection of the panicogenic CCKB receptor agonist pentagastrin (0.002–80 µg/kg) evoked a dose‐related increase in blood pressure, heart rate and ventilation. The response was blocked in the presence of the selective CCKB receptor antagonist CR2945 (1 mg/kg i.v.). The same pattern of cardiovascular and respiratory changes was evoked by microinjection of pentagastrin (0.3 nmol in 250 nL) into the dorsal half of the periaqueductal grey matter (PAG). The effect of intra‐PAG administration of pentagastrin was also abolished following injection of CR2945 (1 mg/kg, i.v.). Responsiveness to systemically administered pentagastrin was enhanced in rats in late dioestrus. At the highest dose tested (80 µg/kg), the pressor response, tachycardia and tachypnoea evoked in rats in late dioestrus was significantly higher than rats in proestrus. For rats in oestrus, the pressor response and tachycardia but not tachypnoea were also significantly larger than the response evoked in rats in early dioestrus. The results suggest that the dorsal half of the PAG (dPAG) plays a key role in mediating the cardiovascular and respiratory responses evoked by systemically administered CCKB agonists. The enhanced responsiveness to panicogenic agents during late dioestrus may be related to changes in the functional responsiveness of γ‐aminobutyric acid (GABA)ergic circuitry in the dPAG due to plasticity of GABAA receptor subunit expression as a consequence of falling progesterone levels.
Complex Segregation Analysis Accounting for GxE of Bone Mineral Density in European Pedigrees Selected Through a Male Proband with Low BMD
Authors: Pelat C. , Van Pottelbergh I. , Cohen‐Solal M. , Ostertag A. , Kaufman J.‐M. , Martinez M. , De Vernejoul M.‐C. 
Published: June 2006

SummaryOsteoporosis is a common multifactorial disorder characterized by low bone mass (BMD) and high susceptibility to low‐trauma fractures. Family and twin studies have found a strong genetic component in the determination of BMD, but the mode of inheritance of this trait is not yet fully understood. BMD is a complex trait whose expression is confounded by environmental influences and polygenic inheritance. Detection of potential gene‐environment interactions is of great interest in the determination of bone health status. Here we have conducted segregation analyses, using the regressive class D models, in a sample of 100 European pedigrees (NEMO) with 713 subjects (524 measured for phenotypes) identified via a male with low BMD values at either the Lumbar Spine or the Femoral Neck. Segregation analyses were conducted on the residuals of LS‐BMD and FN‐BMD adjusted for gender, age and BMI. We tested for gene‐covariate (GxE) interactions, and investigated the impact of significant GxE interactions on segregation results. Without GxE a major effect was found to be marginally significant in LS‐BMD and highly significant in FN‐BMD. For both traits the Mendelian hypothesis was rejected. Significant Age × gene and BMI × gene interactions were revealed. Accounting for GxE increased statistical evidence for a major factor in LS‐BMD, and improved the fit of the data to the Mendelian transmission model for both traits. The best fitting models suggested a codominant major gene accounting for 45% (LS‐BMD) and 44% (FN‐BMD) of the adjusted BMDs. However, substantial residual correlations were also found, and these remained highly significant after accounting for the major gene.
Phosphorylation of rat brain mitochondrial voltage‐dependent anion as a potential tool to control leakage of cytochrome c
Authors: Banerjee Jyotirmoy , Ghosh Subhendu 
Published: June 2006

AbstractApoptosis is a controlled form of cell death that participates in development, elimination of damaged cells and maintenance of cell homeostasis. Also, it plays a role in neurodegenerative disorders like Alzheimer's disease. Recently, mitochondria have emerged as being pivotal in controlling apoptosis. They house a number of apoptogenic molecules, such as cytochrome c, which are released into the cytoplasm at the onset of apoptosis. When rat brain mitochondrial voltage‐dependent anion channel (VDAC), an outer mitochondrial membrane protein, interacts with Bcl‐2 family proteins Bax and tBid, its pore size increases, leading to the release of cytochrome c and other apoptogenic molecules into the cytosol and causing cell death. Regulation of this tBid‐ and Bax‐induced increase in pore size of VDAC is a significant step to control cell death induced by cytochrome c. In this work, we have shown, through bilayer electrophysiological experiments, that the increase in VDAC conductance as a result of its interaction with Bax and tBid is reduced because of the action of cyclic AMP‐dependent protein kinase A (PKA) in the presence of ATP. This indicates that the increase in the pore size of VDAC after its interaction with Bax and tBid is controlled via phosphorylation of this channel by PKA. This, we believe, could be a mechanism of controlling cytochrome c‐mediated cell death in living cells.
Common molecular mechanisms in explicit and implicit memory
Authors: Barco Angel , Bailey Craig H. , Kandel Eric R. 
Published: June 2006

AbstractCellular and molecular studies of both implicit and explicit memory suggest that experience‐dependent modulation of synaptic strength and structure is a fundamental mechanism by which these memories are encoded and stored within the brain. In this review, we focus on recent advances in our understanding of two types of memory storage: (i) sensitization in Aplysia, a simple form of implicit memory, and (ii) formation of explicit spatial memories in the mouse hippocampus. These two processes share common molecular mechanisms that have been highly conserved through evolution.
Enhanced cortical and accumbal molecular reactivity associated with conditioned heroin, but not sucrose‐seeking behaviour
Authors: Koya E. , Spijker Sabine , Voorn Pieter , Binnekade Rob , Schmidt E. Donne , Schoffelmeer Anton N. M. , De Vries Taco J. , Smit August B. 
Published: June 2006

AbstractRe‐exposure to drug‐related cues elicits drug‐seeking behaviour and relapse in both humans and laboratory animals even after months of abstinence. Identifying neural and molecular substrates underlying conditioned heroin‐seeking behaviour will be helpful in understanding mechanisms behind opiate relapse. In humans and animals, brain areas activated by natural reward‐related stimuli (e.g. food, sex) do not show a complete overlap with those activated by stimuli associated with drugs of abuse, suggesting the involvement of different circuitry. To that end, we investigated neural reactivity by measuring immediate early gene (IEG) expression patterns in mesocorticolimbic system target areas following cue‐induced reinstatement of heroin seeking and compared those IEG expression patterns to what was measured during natural reward (sucrose)‐seeking behaviour. Animals were trained to administer heroin associated with a compound audio‐visual cue. Re‐exposure to the cue after 3 weeks of withdrawal reinstated heroin‐seeking behaviour, which resulted in IEG expression of ania‐3, MKP‐1, c‐fos and Nr4a3 in the medial prefrontal cortex (mPFC), and of ania‐3 in the orbital frontal cortex (OFC) and nucleus accumbens core (NAC). The expression patterns for heroin‐seeking behaviours did not generalize to sucrose‐seeking behaviours, indicating that the two behaviours involve different connectivity pathways of neuronal signalling.
GRK1 and GRK7: Unique cellular distribution and widely different activities of opsin phosphorylation in the zebrafish rods and cones
Authors: Wada Yasutaka , Sugiyama Junichi , Okano Toshiyuki , Fukada Yoshitaka 
Published: June 2006

AbstractRetinal cone cells exhibit distinctive photoresponse with a more restrained sensitivity to light and a more rapid shutoff kinetics than those of rods. To understand the molecular basis for these characteristics of cone responses, we focused on the opsin deactivation process initiated by G protein‐coupled receptor kinase (GRK) 1 and GRK7 in the zebrafish, an animal model suitable for studies on retinal physiology and biochemistry. Screening of the ocular cDNAs identified two homologs for each of GRK1 (1A and 1B) and GRK7 (7–1 and 7–2), and they were classified into three GRK subfamilies, 1 A, 1B and 7 by phylogenetic analysis. In situ hybridization and immunohistochemical studies localized both GRK1B and GRK7‐1 in the cone outer segments and GRK1A in the rod outer segments. The opsin/GRKs molar ratio was estimated to be 569 in the rod and 153 in the cone. The recombinant GRKs phosphorylated light‐activated rhodopsin, and the Vmax value of the major cone subtype, GRK7‐1, was 32‐fold higher than that of the rod kinase, GRK1A. The reinforced activity of the cone kinase should provide a strengthened shutoff mechanism of the light‐signaling in the cone and contribute to the characteristics of the cone responses by reducing signal amplification efficiency.
Gene–environment interactions in sporadic Parkinson's disease
Authors: BenMoyal‐Segal Liat , Soreq Hermona 
Published: June 2006

AbstractMuch has been learned in recent years about the genetics of familial Parkinson's disease. However, far less is known about those malfunctioning genes which contribute to the emergence and/or progression of the vast majority of cases, the ‘sporadic Parkinson’s disease', which is the focus of our current review. Drastic differences in the reported prevalence of Parkinson's disease in different continents and countries suggest ethnic and/or environmental‐associated multigenic contributions to this disease. Numerous association studies showing variable involvement of multiple tested genes in these distinct locations support this notion. Also, variable increases in the risk of Parkinson's disease due to exposure to agricultural insecticides indicate complex gene–environment interactions, especially when genes involved in protection from oxidative stress are explored. Further consideration of the brain regions damaged in Parkinson's disease points at the age‐vulnerable cholinergic‐dopaminergic balance as being involved in the emergence of sporadic Parkinson's disease in general and in the exposure‐induced risks in particular. More specifically, the chromosome 7 ACHE/PON1 locus emerges as a key region controlling this sensitive balance, and animal model experiments are compatible with this concept. Future progress in the understanding of the genetics of sporadic Parkinson's disease depends on globally coordinated, multileveled studies of gene–environment interactions.
Hypoxic damage to the periventricular white matter in neonatal brain: role of vascular endothelial growth factor, nitric oxide and excitotoxicity
Authors: Kaur Charanjit , Sivakumar Viswanathan , Ang Lin Stella , Sundaresan Alamelu 
Published: June 2006

AbstractThe present study examined factors that may be involved in the development of hypoxic periventricular white matter damage in the neonatal brain. Wistar rats (1‐day old) were subjected to hypoxia and the periventricular white matter (corpus callosum) was examined for the mRNA and protein expression of hypoxia‐inducible factor‐1α (HIF‐1α), endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS and iNOS), vascular endothelial growth factor (VEGF) and N‐methyl‐D‐aspartate receptor subunit 1 (NMDAR1) between 3 h and 14 days after hypoxic exposure by real‐time RT‐PCR, western blotting and immunohistochemistry. Up‐regulated mRNA and protein expression of HIF‐1α, VEGF, NMDAR1, eNOS, nNOS and iNOS in corpus callosum was observed in response to hypoxia. NMDAR1 and iNOS expression was found in the activated microglial cells, whereas VEGF was localized to astrocytes. An enzyme immunoassay showed that the VEGF concentration in corpus callosum was significantly higher up to 7 days after hypoxic exposure. NO levels, measured by colorimetric assay, were also significantly higher in hypoxic rats up to 14 days after hypoxic exposure as compared with the controls. A large number of axons undergoing degeneration were observed between 3 h and 7 days after the hypoxic exposure at electron‐microscopic level. Our findings point towards the involvement of excitotoxicity, VEGF and NO in periventricular white matter damage in response to hypoxia.
Genetic vitamin E deficiency does not affect MPTP susceptibility in the mouse brain
Authors: Ren Yong‐Ri , Nishida Yoichiro , Yoshimi Kenji , Yasuda Toru , Jishage Kou‐ichi , Uchihara Toshiki , Yokota Takanori , Mizuno Yoshikuni , Mochizuki Hideki 
Published: June 2006

AbstractOxidative stress is involved in the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). Vitamin E (alpha‐tocopherol) is a potent antioxidant in the cell membrane that can trap free radicals and prohibit lipid peroxidation. The retention and secretion of vitamin E are regulated by alpha‐tocopherol transfer protein (TTP) in the brain and liver. Dysfunction of TTP results in systemic deficiency of vitamin E in humans and mice, and increased oxidative stress in mouse brain. In this study, we investigated the effect of vitamin E deficiency in PD development by generating an 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of PD using TTP knockout (TTP–/–) mice. Vitamin E concentration in the brains of TTP+/– mice was half that in TTP+/+ mice, and in TTP–/– mice, was undetectable. MPTP treatment tended to decrease striatal dopamine, but the effect was comparable and not significant in any of the three genotypes. Furthermore, the extent of loss of dopaminergic cell bodies in the substantia nigra did not differ among the groups. One the other hand, oral administration of vitamin E resulted in the partial protection of striatal dopaminergic terminals against MPTP toxicity. Our results suggest that vitamin E does not play a major protective role in MPTP‐induced nigrostriatal dopaminergic neurodegeneration in the brain.
Intrinsic and extrinsic determinants of ion channel localization in neurons
Authors: Hedstrom Kristian L. , Rasband Matthew N. 
Published: June 2006

AbstractNeurons are an extremely diverse group of excitable cells with a wide variety of morphologies including complex dendritic trees and very long axons. The electrical properties of neurons depend not only on the types of ion channels and receptors expressed, but also on where these channels are located in the cell. Two extreme examples that illustrate the subcellular polarized nature of neurons and the tight regulation of ion channel localization can be seen at the axon initial segment and the node of Ranvier. The axon initial segment is important for initiation of action potentials in the axon, whereas the node of Ranvier is required for the rapid, faithful and efficient propagation of action potentials along the axon. Given the similarity of their functions it is not surprising that nearly every protein component of the axon initial segment is also found at the node. However, there is one very important difference between these two sites: nodes require extrinsic, glial‐derived factors in order to form, whereas the axon initial segment is intrinsically determined by the neuron. This mini‐review discusses recent results that have begun to clarify the intrinsic and extrinsic mechanisms underlying formation of nodes and axon initial segments, and poses several important unanswered questions regarding their unique mechanisms of formation.
The effects of stress on muscarinic receptors. Heterologous receptor regulation: yes or no?
Authors: Mysliveček J. , Kvetňanský R. 
Published: June 2006

Summary1 Stress is usually comprehended as an event affecting mainly the catecholaminergic system, the hypothalamo–pituitary–adrenocortical (HPA) axis and the receptor systems connected to these neurotransmitters/hormones. Other neurotransmitter/hormone systems can be affected too. Here we review the available data on the effects of different stressful stimuli (physical, chemical, psychological/social, cardiovascular, affecting multiple system) on muscarinic receptors (MR).2 The data suppose the existence of specific mechanisms that regulate the signalization through MR during different type of stress.3 Physical stressors (coldvs. heat) reveal opposite type of changes on peripheral‐tissue MRs. Chemical stressors (oxidative stress) are tightly connected with MR and it is especially interesting that the sensitivity of MR to oxidative stress is subtype‐specific. It is also suggested that heterologous regulation can occur with psychological/social stressors on the organism. Cardiovascular system‐disturbing stressors cause disbalance between autonomic receptors or down‐regulate MR in the peripheral tissue. Immobilization caused opposite effects on MR in the central nervous system and periphery, where the changes are supposed to be due to heterologous regulation between receptor systems.4 In conclusion, some data indicate that in specific conditions MR are regulated as a consequence of other changes rather than as a primary effect of stress. On the contrary, in some situations, MR are the first targets to respond to the stress.5 These findings on stress‐induced activity of the cholinergic system and changes in muscarinic receptors support the view that stress is a specific response of the organism.