bluuebunny/crossref_metadata_2025_split huggingface dataset:
Good genes, genetic compatibility and the evolution of polyandry: use of the diallel cross to address competing hypotheses
Authors: IVY T. M. 
Published: December 2006

AbstractGenetic benefits can enhance the fitness of polyandrous females through the high intrinsic genetic quality of females’ mates or through the interaction between female and male genes. I used a full diallel cross, a quantitative genetics design that involves all possible crosses among a set of genetically homogeneous lines, to determine the mechanism through which polyandrous female decorated crickets (Gryllodes sigillatus) obtain genetic benefits. I measured several traits related to fitness and partitioned the phenotypic variance into components representing the contribution of additive genetic variance (‘good genes’), nonadditive genetic variance (genetic compatibility), as well as maternal and paternal effects. The results reveal a significant variance attributable to both nonadditive and additive sources in the measured traits, and their influence depended on which trait was considered. The lack of congruence in sources of phenotypic variance among these fitness‐related traits suggests that the evolution and maintenance of polyandry are unlikely to have resulted from one selective influence, but rather are the result of the collective effects of a number of factors.
Single nucleotide polymorphism profiling assay to exclude serum sample mix‐up
Authors: Huijsmans C. J. J. , Heilmann F. G. C. , Van Der Zanden A. G. M. , Schneeberger P. M. , Hermans M. H. A. 
Published: December 2006

Background and Objectives  Sample mix‐ups are a threat to the validity of clinical laboratory test results. To detect serum sample mix‐ups we developed a single nucleotide polymorphism (SNP) profiling test. SNPs are frequent sequence variations in the human genome. Each individual has a unique combination of these nucleotide variations.Materials and Methods  Predeveloped SNP amplification assays are commercially available. We recently discovered that these SNP assays could be applied to serological samples, which is not self‐evident because a key step in serum preparation is removal of white blood cells, the major source of DNA, from blood. DNA was extracted from serum samples. Real‐time polymerase chain reaction (PCR) analysis of the purified DNA using a selection of 10 SNP assays provided SNP profiles.Results  The applicability of the SNP profiling test was demonstrated by means of a case where hepatitis E virus serological determinations of four serum samples of one patient seemed inconsistent. SNP profiling of the samples demonstrated that this was due to the enzyme‐linked immunosorbent assay test instead of sample mix‐up.Conclusion  We have developed an SNP profiling assay that provides a way to link human serum samples to a source, without post‐PCR processing. The chance for two randomly chosen individuals to have an identical profile is 1 in 18 000. Solving potential serum sample mix‐ups will secure downstream evaluations and critical decisions concerning the patients involved.
The interaction between prion protein and laminin modulates memory consolidation
Authors: Coitinho Adriana S. , Freitas Adriana R. O. , Lopes Marilene H. , Hajj Glaucia N. M. , Roesler Rafael , Walz Roger , Rossato Janine I. , Cammarota Martin , Izquierdo Ivan , Martins Vilma R. , Brentani Ricardo R. 
Published: December 2006

AbstractCellular prion protein (PrPc) has a pivotal role in prion diseases. PrPc is a specific receptor for laminin (LN) γ1 peptide and several lines of evidence indicate that it is also involved in neural plasticity. Here we investigated whether the interaction between PrPc and LN plays a role in rat memory formation. We found that post‐training intrahippocampal infusion of PrPc‐derived peptides that contain the LN binding site ( and ) or of anti‐PrPc or anti‐LN antibodies that inhibit PrPc–LN interaction impaired inhibitory avoidance memory retention. The amnesic effect of anti‐PrPc antibodies and peptide was reversed by co‐infusion of a LN γ1 chain‐derived peptide containing the PrPc‐binding site, suggesting that PrPc–LN interaction is indeed crucial for memory consolidation. In addition, peptide and anti‐PrPc or anti‐LN antibodies also inhibited the activation of hippocampal cAMP‐dependent protein kinase A (PKA) and extracellular regulated kinase (ERK1/2), two kinases that mediate the up‐regulation of signaling pathways needed for consolidation of inhibitory avoidance memory. Our findings show that, through its interaction with LN, hippocampal PrPc plays a critical role in memory processing and suggest that this role is mediated by activation of both PKA and ERK1/2 signaling pathways.
Morphological and cellular changes within embryonic striatal grafts associated with enriched environment and involuntary exercise
Authors: Döbrössy Máté D. , Dunnett Stephen B. 
Published: December 2006

AbstractEnvironmental enrichment (EE) and exercise have been implicated in influencing behaviour and altering neuronal processes associated with cellular morphology in both ‘normal’ and injured states of the CNS. Using a rodent model of Huntington's disease, we investigated whether prolonged EE or involuntary exercise can induce morphological and cellular changes within embryonic striatal transplants. Adult rats were trained on the Staircase test – requiring fine motor control to reach and collect reward pellets – prior to being lesioned unilaterally in the dorsal neostriatum with quinolinic acid. The lesioned animals received E15 whole ganglionic eminence cell suspension grafts followed by housing in EE or standard cages. Half of the animals in standard cages received daily forced exercise on a treadmill. The grafted animals showed significant functional recovery on both the Staircase test and in drug‐induced rotation. Neither the housing conditions nor the training had an impact on the behaviour, with the exception of the treadmill reducing the ipsilateral drug‐induced rotation observed amongst the lesioned animals. However, the animals housed in the EE had significantly increased striatal brain‐derived neurotrophic factor (BDNF) levels, and graft neurons in these animals exhibited both greater spine densities and larger cell volumes. Animals on forced exercise regime had reduced BDNF levels and grafted cells with sparser spines. The study suggests that the context of the animal can affect the plasticity of transplanted cells. Appropriately exploiting the underlying, and yet unknown, mechanisms could lead the way to improved anatomical and potentially functional integration of the graft.
Differential expression of active zone proteins in neuromuscular junctions suggests functional diversification
Authors: Juranek Judyta , Mukherjee Konark , Rickmann Michael , Martens Henrik , Calka Jaroslaw , Südhof Thomas C. , Jahn Reinhard 
Published: December 2006

AbstractNerve terminals of the central nervous system (CNS) contain specialized release sites for synaptic vesicles, referred to as active zones. They are characterized by electron‐dense structures that are tightly associated with the presynaptic plasma membrane and organize vesicle docking and priming sites. Recently, major protein constituents of active zones have been identified, including the proteins Piccolo, Bassoon, RIM, Munc13, ERCs/ELKs/CASTs and liprins. While it is becoming apparent that each of these proteins is essential for synaptic function in the CNS, it is not known to what extent these proteins are involved in synaptic function of the peripheral nervous system. Somatic neuromuscular junctions contain morphologically and functionally defined active zones with similarities to CNS synapses. In contrast, sympathetic neuromuscular varicosities lack active zone‐like morphological specializations. Using immunocytochemistry at the light and electron microscopic level we have now performed a systematic investigation of all five major classes of active zone proteins in peripheral neuromuscular junctions. Our results show that somatic neuromuscular endplates contain a full complement of all active zone proteins. In contrast, varicosities of the vas deferens contain a subset of active zone proteins including Bassoon and ELKS2, with the other four components being absent. We conclude that Bassoon and ELKS2 perform independent and specialized functions in synaptic transmission of autonomic synapses.
Docosahexaenoic acid (22:6n‐3) enrichment of membrane phospholipids increases gap junction coupling capacity in cultured astrocytes
Authors: Champeil‐Potokar Gaelle , Chaumontet Catherine , Guesnet Philippe , Lavialle Monique , Denis Isabelle 
Published: December 2006

AbstractAlthough it is agreed that n‐3 polyunsaturated fatty acids (PUFAs) are important for brain function, it has yet to be demonstrated how they are involved in precise cellular mechanisms. We investigated the role of enhanced n‐3 PUFA in astrocyte membranes on the gap junction capacity of these cells. Astrocytes isolated from newborn rat cortices were grown in medium supplemented with docosahexaenoic acid (DHA), the main n‐3 PUFA in cell membranes, or arachidonic acid (AA), the main n‐6 PUFA, plus an antioxidant (α‐tocopherol or N‐acetyl‐cystein) to prevent peroxidation. The resulting three populations of astrocytes differed markedly in their n‐3 : n‐6 PUFA ratios in phosphatidylethanolamine and phosphatidylcholine, the main phospholipids in membranes. DHA‐supplemented cells had a physiological high n‐3 : n‐6 ratio (1.58), unsupplemented cells had a low n‐3 : n‐6 ratio (0.66) and AA‐supplemented cells had a very low n‐3 : n‐6 ratio (0.36), with excess n‐6 PUFA. DHA‐supplemented astrocytes had a greater gap junction capacity than unsupplemented cells or AA‐supplemented cells. The enhanced gap junction coupling of DHA‐enriched cells was associated with a more functional distribution of connexin 43 at cell interfaces (shown by immunocytochemistry) and more of the main phosphorylated isoform of connexin 43. These findings suggest that the high n‐3 : n‐6 PUFA ratio that occurs naturally in astrocyte membranes is needed for optimal gap junction coupling in these cells.
Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4‐1.1/Kvβ1.1 and Kv1.4‐1.1/Kvβ1.2
Authors: Imbrici Paola , D'Adamo Maria Cristina , Kullmann Dimitri M. , Pessia Mauro 
Published: December 2006

AbstractEpisodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by constant muscle rippling movements (myokymia) and episodic attacks of ataxia. Several heterozygous point mutations have been found in the coding sequence of the voltage‐gated potassium channel gene KCNA1 (hKv1.1), which alter the delayed‐rectifier function of the channel. Shaker‐like channels of different cell types may be formed by unique hetero‐oligomeric complexes comprising Kv1.1, Kv1.4 and Kvβ1.x subunits. Here we show that the human Kvβ1.1 and Kvβ1.2 subunits modulated the functional properties of tandemly linked Kv1.4‐1.1 wild‐type channels expressed in Xenopus laevis oocytes by (i) increasing the rate and amount of N‐type inactivation, (ii) slowing the recovery rate from inactivation, (iii) accelerating the cumulative inactivation of the channel and (iv) negatively shifting the voltage dependence of inactivation. To date, the role of the human Kv1.4‐1.1, Kv1.4‐1.1/Kvβ1.1 and Kv1.4‐1.1/Kvβ1.2 channels in the aetiopathogenesis of EA1 has not been investigated. Here we also show that the EA1 mutations E325D, V404I and V408A, which line the ion‐conducting pore, and I177N, which resides within the S1 segment, alter the fast inactivation and repriming properties of the channels by decreasing both the rate and degree of N‐type inactivation and by accelerating the recovery from fast inactivation. Furthermore, the E325D, V404I and I177N mutations shifted the voltage dependence of the steady‐state inactivation to more positive potentials. The results demonstrate that the human Kvβ1.1 and Kvβ1.2 subunits regulate the proportion of wild‐type Kv1.4‐1.1 channels that are available to open. Furthermore, EA1 mutations alter heteromeric channel availability which probably modifies the integration properties and firing patterns of neurones controlling cognitive processes and body movements.
Glutamate‐mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR‐induced release of Ca++ from intracellular stores and is prevented by estradiol
Authors: Hilton Genell D. , Nunez Joseph L. , Bambrick Linda , Thompson Scott M. , McCarthy Margaret M. 
Published: December 2006

AbstractHypoxic/ischemic (HI) brain injury in newborn full‐term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also released following HI, but neurons are largely insensitive to NMDA or AMPA/kainic acid (KA) receptor‐mediated damage. Using primary cultured hippocampal neurons we have determined that glutamate increases intracellular calcium much more than kainic acid. Moreover, glutamate induces cell death by activating Type I metabotropic glutamate receptors (mGluRs). Pretreatment of neurons with the gonadal steroid estradiol reduces the level of the Type I metabotropic glutamate receptors and completely prevents cell death, suggesting a novel therapeutic approach to excitotoxic brain damage in the neonate.
Properties of cholinergic responses in neurons in the intermediate grey layer of rat superior colliculus
Authors: Sooksawate Thongchai , Isa Tadashi 
Published: December 2006

AbstractThe intermediate grey layer (SGI) of superior colliculus (SC) receives cholinergic innervation from brainstem parabrachial region. To clarify the action of cholinergic inputs to local circuits in the SGI, we investigated the effect of cholinergic agonists and antagonists on a large number of randomly sampled neurons in Wistar rat SGI (n = 246) using whole‐cell patch clamp technique in slices of the rat SC. Responses of the recorded cells (n = 98) to bath application of carbachol were classified into five patterns: (i) nicotinic inward only (n = 14); (ii) nicotinic inward + muscarinic inward (n = 26); (iii) nicotinic inward + muscarinic inward + muscarinic outward (n = 39); (iv) nicotinic inward + muscarinic outward (n = 13) and (v) muscarinic outward only (n = 4). Among these, a majority of morphologically identified projection neurons exhibited either response pattern (ii) (9/28) or (iii) (15/28), which suggested that the primary action of cholinergic inputs on the SGI output is excitatory. Nicotinic receptor subtypes involved in the nicotinic current were examined by testing the effects of antagonists on the currents induced by bath application of 1,1‐dimethyl‐4‐phenyl‐piperazinium or transient pressure application of acetylcholine (ACh). Muscarinic receptor subtypes involved in the muscarinic inward and outward currents were investigated by examining the effects of antagonists on muscarine‐induced currents. The results showed that nicotinic inward currents are mediated mainly by α4β2 and partly by α7 nicotinic receptors and that muscarinic inward and outward currents are mediated by M3 (plus M1) and M2 muscarinic receptors, respectively.
A CaV2.1 calcium channel mutation rocker reduces the number of postsynaptic AMPA receptors in parallel fiber–Purkinje cell synapses
Authors: Kodama Takashi , Itsukaichi‐Nishida Yuko , Fukazawa Yugo , Wakamori Minoru , Miyata Mariko , Molnar Elek , Mori Yasuo , Shigemoto Ryuichi , Imoto Keiji 
Published: December 2006

AbstractThe rocker mice are hereditary ataxic mutants that carry a point mutation in the gene encoding the CaV2.1 (P/Q‐type) Ca2+ channel α1 subunit, and show the mildest symptoms among the reported CaV2.1 mutant mice. We studied the basic characteristics of the rocker mutant Ca2+ channel and their impacts on excitatory synaptic transmission in cerebellar Purkinje cells (PCs). In acutely dissociated PC somas, the rocker mutant channel showed a moderate reduction in Ca2+ channel current density, whereas its kinetics and voltage dependency of gating remained nearly normal. Despite the small changes in channel function, synaptic transmission in the parallel fiber (PF)–PC synapses was severely impaired. The climbing fiber inputs onto PCs showed a moderate impairment but could elicit normal complex spikes. Presynaptic function of the PF–PC synapses, however, was unexpectedly almost normal in terms of paired‐pulse facilitation, sensitivity to extracellular Ca2+ concentration and glutamate concentration in synaptic clefts. Electron microscopic analyses including freeze‐fracture replica labeling revealed that both the number and density of postsynaptic α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors substantially decreased without gross structural changes of the PF–PC synapses. We also observed an abnormal arborization of PC dendrites in young adult rocker mice (∼ 1 month old). These lines of evidence suggest that even a moderate dysfunction of CaV2.1 Ca2+ channel can cause substantial changes in postsynaptic molecular composition of the PF–PC synapses and dendritic structure of PCs.
Neuroprotection in Parkinson models varies with toxin administration protocol
Authors: Anderson David W. , Bradbury Kristin A. , Schneider Jay S. 
Published: December 2006

AbstractNumerous factors contribute to substantia nigra pars compacta (SNc) dopamine (DA) neuron death in Parkinson's disease (PD), thus complicating the search for effective neuroprotective agents for this disease. Although the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mouse has been widely used for assessing neuroprotective agents for PD, the pathological processes resulting from MPTP exposure can vary greatly depending upon the MPTP administration protocol. This study assessed the degree to which the neuroprotective efficacy of particular agents may depend upon the MPTP administration protocol (i.e. acute vs. subacute toxin administration). Endpoints analysed were changes in tyrosine hydroxylase (TH) and NeuN cell numbers in the SNc, striatal DA and metabolite levels, and striatal TH+fiber density. The efficacy of putative neuroprotective agents [i.e. LIGA 20, nicotinamide and pramipexole (PPX)] varied depending upon the MPTP administration protocol. LIGA 20 spared striatal DA levels in both MPTP models, while nicotinamide was only effective in the acute toxin administration model and PPX was only effective in the subacute model. In both MPTP models, LIGA 20 and nicotinamide significantly spared DAergic neurons; PPX only spared DAergic neurons in the subacute model. Only acute MPTP‐treated mice that received nicotinamide had a significant sparing of striatal DAergic fibers. These results underscore the need to assess putative neuroprotective agents for PD in multiple animal models using multiple endpoints. This strategy may better identify compounds with broad neuroprotective/neurorestorative profiles that may be more likely to be clinically effective.
Secreted factors from ventral telencephalon induce the differentiation of GABAergic neurons in cortical cultures
Authors: Trinh H.‐h. , Reid J. , Shin E. , Liapi A. , Parnavelas J. G. , Nadarajah B. 
Published: December 2006

AbstractIt is widely believed that the pyramidal cells and interneurons of the cerebral cortex are distinct in their origin, lineage and genetic make up. In view of these findings, the current thesis is that the phenotype determination of cortical neurons is primarily directed by genetic mechanisms. Using in vitro assays, the present study demonstrates that secreted factors from ganglionic eminence (GE) of the ventral telencephalon have the potency to induce the differentiation of a subset of cortical neurons towards γ‐aminobutyric acid (GABA)ergic lineage. Characterization of cortical cultures that were exposed to medium derived from GE illustrated a significant increase in the number of GABA‐, calretinin‐ and calbindin‐positive neurons. Calcium imaging together with pharmacological studies showed that the application of exogenous medium significantly elevated the intracellular calcium transients in cortical neurons through the activation of ionotropic glutamate receptors. The increase in GABA+ neurons appeared to be associated with the elevated calcium activity; treatment with blockers specific for glutamate receptors abolished both the synchronized transients and reduced the differentiation of GABAergic neurons. Such studies demonstrate that although intrinsic mechanisms determine the fate of cortical interneurons, extrinsic factors have the potency to influence their neurochemical differentiation and contribute towards their molecular diversity.
Dopamine activity in the nucleus accumbens modulates blocking in fear conditioning
Authors: Iordanova Mihaela D. , Westbrook R. Frederick , Killcross A. Simon 
Published: December 2006

AbstractAssociative learning depends on the discrepancy between actual and predicted outcomes. The neurochemical mechanisms involved in regulating this discrepancy in Pavlovian fear conditioning in rats are unknown. We employed the blocking paradigm to show that this learning discrepancy is decreased by heightened activation of dopamine following an accumbal infusion of d‐amphetamine, and increased by dopaminegic blockade following an accumbal infusion of cis‐(z)‐flupenthixol or by combined infusions of the D1 (SCH23390) and D2 (sulpiride) antagonists but not by infusion of either alone.
Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti‐myelin‐associated glycoprotein antibody
Authors: Thompson Hilaire J. , Marklund Niklas , LeBold David G. , Morales Diego M. , Keck Carrie A. , Vinson Mary , Royo Nicolas C. , Grundy Robert , McIntosh Tracy K. 
Published: December 2006

AbstractAxonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin‐associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG‐specific monoclonal antibody (mAb). Anesthetized rats (n = 102) were subjected to either lateral fluid percussion brain injury (n = 59) or sham injury (n = 43). In surviving animals, beginning at 1 h post‐injury, 8.64 µg anti‐MAG mAb (n = 33 injured, n = 21 sham) or control IgG (n = 26 injured, n = 22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n = 14 sham, n = 11 injured) was killed at 72 h post‐injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post‐injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post‐injury. At 72 h post‐injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain‐injured animals, and anti‐MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain‐injured animals receiving anti‐MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P < 0.01) post‐injury when compared with brain‐injured IgG‐treated animals. Additionally, at 8 weeks post‐injury, the anti‐MAG mAb‐treated brain‐injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P < 0.05) when compared with their brain‐injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.