bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide‐dependent long‐term potentiation revealed by real‐time imaging of nitric oxide production and neuronal excitation in the dorsal horn of rat spinal cord slices
Authors: Ikeda Hiroshi , Kusudo Kei , Murase Kazuyuki 
Published: April 2006

AbstractNitric oxide (NO) is thought to be involved in the central mechanism of hyperalgesia and allodynia at the spinal level. Recently, we reported that NO played an important role in the induction of long‐term potentiation (LTP) of synaptic strength in spinal dorsal horn, which is believed to underlie hyperalgesia and allodynia. In this study, to elucidate the relationship of NO to LTP in spinal dorsal horn, we measured the spatiotemporal distribution of NO signal with the NO‐sensitive dye, DAR‐4M, and neuronal excitation with the voltage‐sensitive dye, RH482, in rat spinal cord slices, elicited by dorsal root stimulation. In superficial dorsal horn, neuronal excitation evoked by C fiber‐activating dorsal root stimulation was potentiated for more than 2 h after low‐frequency conditioning stimulation (LFS, 240 pulses at 2 Hz for 2 min). In the same slices that exhibited LTP, NO was produced and distributed in the superficial dorsal horn during the delivery of LFS, and the amplitude of LTP and amount of NO production showed close correlation from slice to slice. LTP and production of NO were inhibited in the presence of the NO synthase inhibitors and an inhibitor of heme oxygenase, the synthetic enzyme for carbon monoxide (CO). These results suggest that production and distribution of NO is necessary for the induction of LTP in spinal dorsal horn, and that CO contributes to the LTP induction and NO production by LFS.
Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease
Authors: Kühn Andrea A. , Kupsch Andreas , Schneider Gerd‐Helge , Brown Peter 
Published: April 2006

AbstractStrong synchronization of neuronal activity occurs in the 8–35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8–35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep‐brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8–35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60–90 Hz band, if present (seven sides, on medication). Levodopa‐induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8–35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia‐rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60–90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency‐specific. Our results support a link between levodopa‐induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.
MPTP treatment of common marmosets impairs proteasomal enzyme activity and decreases expression of structural and regulatory elements of the 26S proteasome
Authors: Zeng B‐Y. , Iravani M. M. , Lin S‐T. , Irifune M. , Kuoppamäki M. , Al‐Barghouthy G. , Smith L. , Jackson M. J. , Rose S. , Medhurst A. D. , Jenner P. 
Published: April 2006

AbstractDysfunction of the ubiquitin‐proteasome system occurs in the substantia nigra (SN) in Parkinson's disease (PD). However, it is unknown whether this is a primary cause or a secondary consequence of other components of the pathogenic process. We have investigated in nonhuman primates whether initiating cell death through mitochondrial complex I inhibition using 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride (MPTP) altered proteasomal activity or the proteasomal components in the SN. Chymotrypsin‐like, trypsin‐like and peptidylglutamyl‐peptide hydrolase (PGPH) activating of 20S proteasome were decreased in SN homogenates of MPTP‐treated marmosets compared to naïve animals. Western blotting revealed a marked decrease in the expression of 20S‐α subunits, but no change in 20S‐β subunits in the SN of MPTP‐treated marmoset compared to naïve animals. There was a marked decrease in the expression of the proteasome activator 700 (PA700) and proteasome activator 28 (PA28) regulatory complexes. The 20S‐α4 subunit immunoreactivity was decreased in the nucleus of colocalized tyrosine hydroxylase (TH)‐positive cells of MPTP‐treated animals compared to naïve animals but no difference in the intensity of 20S‐β1i subunit staining. Immunoreactivity for PA700‐Rpt5 and PA28‐α subunits within surviving TH‐positive cells of MPTP‐treated marmoset was reduced compared to naïve controls. Overall, the changes in proteasomal function and structure occurring follow MPTP‐induced destruction of the SN in common marmosets were very similar to those found in PD. This suggests that altered proteasomal function in PD could be a consequence of other pathogenic processes occurring in SN as opposed to initiating cell death as previously suggested.
NF‐κB pathway: a target for preventing β‐amyloid (Aβ)‐induced neuronal damage and Aβ42 production
Authors: Valerio Alessandra , Boroni Flora , Benarese Marina , Sarnico Ilenia , Ghisi Valentina , Bresciani Laura Grazia , Ferrario Marina , Borsani Giuseppe , Spano PierFranco , Pizzi Marina 
Published: April 2006

AbstractBeta‐amyloid (Aβ) peptides are key proteins in the pathophysiology of Alzheimer's disease (AD). While Aβ42 aggregates very rapidly to form early diffuse plaques, supplemental Aβ40 deposition is required to form mature neuritic plaques. We here investigated the role of nuclear factor‐κB (NF‐κB) pathway in Aβ40‐mediated neuronal damage and amyloid pathology. In rat primary neurons and human postmitotic neuronal cells, the Aβ peptide induced a dose‐dependent neuronal death, reduced the levels of the anti‐apoptotic protein Bcl‐XL, enhanced the cytosolic release of cytochrome c, and elicited the intracellular accumulation and secretion of Aβ42 oligomers. Moreover, Aβ40 activated the NF‐κB pathway by selectively inducing the nuclear translocation of p65 and p50 subunits, and promoted an apoptotic profile of gene expression. As inhibitors of the NF‐κB pathway, we tested the capability of a double‐stranded κB decoy oligonucleotide, the anti‐inflammatory drug aspirin and the selective IκB kinase 2 inhibitor, AS602868, to modify the Aβ40‐mediated effects. These treatments, transiently applied before Aβ exposure, completely inhibited p50/p65 nuclear translocation and neuronal damage. The κB decoy also inhibited the Aβ‐induced release of cytochrome c, restored the levels of Bcl‐XL, and prevented intraneuronal accumulation and secretion of Aβ42. These results open up interesting perspectives on the development of novel strategies targeting out NF‐κB p50/p65 dimers for pharmacological intervention in AD.
Long‐term stability of fear memory depends on the synthesis of protein but not mRNA in the amygdala
Authors: Parsons Ryan G. , Gafford Georgette M. , Baruch David E. , Riedner Brady A. , Helmstetter Fred J. 
Published: April 2006

AbstractSynaptic modification supporting memory formation is thought to depend on gene expression and protein synthesis. Disrupting either process around the time of learning prevents the formation of long‐term memory. Recent evidence suggests that memory also becomes susceptible to disruption upon retrieval. Whether or not the molecular events involved in the formation of new memory are the same as what is needed for memory to persist after retrieval has yet to be determined. In the present set of experiments, rats were given inhibitors of protein or messenger ribonucleic acid (mRNA) synthesis into the amygdala just after training or retrieval of fear memory. Results showed that blocking mRNA or protein synthesis immediately after learning prevented the formation of long‐term memory, while stability of memory after retrieval required protein, but not mRNA, synthesis. These data suggest that the protein needed for memory reconsolidation after retrieval may be transcribed from pre‐existing stores of mRNA.
Jacobsen Syndrome and Beckwith‐Wiedemann Syndrome Caused by a Parental Pericentric Inversion inv(11)(p15q24)
Authors: Gadzicki D. , Baumer A. , Wey E. , Happel C. M. , Rudolph C. , Tönnies H. , Neitzel H. , Steinemann D. , Welte K. , Klein C. , Schlegelberger B. 
Published: April 2006

SummaryHere we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on 11q23 was lost and replaced by the distal region of 11p, leading to a partial trisomy of 11p and a partial monosomy of 11q. According to ISCN (1995) the karyotype can be described as 46,XY,add(11)(q2?3). ish 11ptel(D11S2071x3),11qtel(VIJyRM2072x1). Array‐CGH analysis allowed us to narrow down the breakpoints to 11p15.1 and 11q24.1. Methylation analyses of genes located on 11p showed an increased level of the non‐methylated paternal allele of the KCNQ1OT1 gene, confirming the concomitant presence of Beckwith‐Wiedemann syndrome (BWS). The phenotype resulting from the 11q deletion seems to dominate the phenotype due to the distal 11p trisomy. Investigation of the parents revealed that this chromosomal rearrangement was caused by a paternal pericentric inversion inv(11)(p15q24).Since chromosomal aberrations like the one described here can easily be overlooked during routine chromosome analysis, combined FISH analysis using subtelomeric and possibly additional probes should be applied if there is any doubt about the integrity of telomeric regions.
G‐Protein β3 Subunit Variant C825T is a Risk Factor for Hypertension in Japanese Females ‐A Prospective Cohort Study Over 5 Years
Authors: Suwazono Y. , Kobayashi E. , Uetani M. , Miura K. , Morikawa Y. , Ishizaki M. , Kido T. , Nakagawa H. , Nogawa K. 
Published: April 2006

SummaryThe relationship between the G‐protein β3 subunit variant C825T and risk of hypertension was examined in a prospective cohort study of Japanese workers. This study included observations over a 5‐year period from 1997 to 2002 on 878 males and 692 females who were normotensive at entry. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or taking antihypertensive medication. Pooled logistic regression analyses were performed using C825T genotype, age, body mass index, lifestyle, and the result of blood chemistries as the covariates. Multivariate pooled logistic regression analysis showed the risk of hypertension was 2.31 times higher in females with the TT genotype than in females with the CC genotype (95% confidence interval: 1.07–4.96), after adjustment for the effects of other potential covariates. In contrast, no significant risk of hypertension was observed with the TT genotype in male subjects. This study indicates that the 825T allele is an independent risk factor for hypertension in Japanese females, and suggests that this polymorphism may be a beneficial prognostic marker for hypertension in the general Japanese female population.
N‐acetylglucosaminyltranferase VB expression enhances β1 integrin‐ dependent PC12 neurite outgrowth on laminin and collagen
Authors: Lee Intaek , Guo Hua‐Bei , Kamar Maria , Abbott Karen , Troupe Karolyn , Lee Jin‐Kyu , Alvarez‐Manilla Gerardo , Pierce Michael 
Published: April 2006

AbstractN‐acetylglucosaminyltransferase VB (GnT‐VB, ‐IX) is a newly discovered glycosyltransferase expressed exclusively in high levels in neuronal tissue during early development. Its homolog, GnT‐V, is expressed in many tissues and modulates cell–cell and cell–matrix adhesion. The ability of GnT‐VB to regulate cell–matrix interactions was initially investigated using the rat pheochromocytoma PC12 neurite outgrowth model. PC12 cells stably transfected with GnT‐VB consistently showed an enhanced rate of nerve growth factor (NGF)‐induced neurite outgrowth on collagen and laminin substrates. Levels of TrkA receptor phosphorylation and downstream ERK activation induced by NGF were not influenced by GnT‐VB expression. No significant difference was observed in the rate of neurite outgrowth when cells were cultured on non‐coated culture dishes, indicating that integrin–ECM interaction is required for the stimulatory effects. Neurite outgrowth induced by manganese‐dependent activation of β1 integrin on collagen and laminin substrates, however, showed a significant increase in neurite length for the PC12/GnT‐VB cells, compared with control cells, suggesting that the enhancement is most likely mediated by alteration of β1 integrin–ECM interaction by GnT‐VB. These results demonstrate that GnT‐VB expression can modulate the rate of neurite outgrowth by affecting β1 integrin–ECM interaction.
Caspase‐dependent alteration of the ADP/ATP translocator triggers the mitochondrial permeability transition which is not required for the low‐potassium‐dependent apoptosis of cerebellar granule cells
Authors: Atlante Anna , Bobba Antonella , De Bari Lidia , Fontana Fabrizio , Calissano Pietro , Marra Ersilia , Passarella Salvatore 
Published: April 2006

AbstractWe investigated ADP/ATP exchange mediated by the adenine nucleotide translocator and opening of the mitochondrial permeability transition pore in homogenates from cerebellar granule cells en route to apoptosis induced by low potassium. We showed that, in the first 3 h of apoptosis, when maximum cytochrome c release had already occurred, adenine nucleotide translocator function was impaired owing to the action of reactive oxygen species, but no permeability transition pore opening occurred. Over 3–8 h of apoptosis, the permeability transition pore progressively opened, owing to caspase action, and further ADP/ATP translocator impairment occurred. The kinetics of transport and permeability transition pore opening were inversely correlated, both in the absence and presence of inhibitors of antioxidant and proteolytic systems. We conclude that, en route to apoptosis, alteration of the adenine nucleotide translocator occurs, resulting in permeability transition pore opening. This process depends on the action of caspase on pore component(s) other than the ADP/ATP translocator, because no change in either amount or molecular weight of the latter protein was noted during apoptosis, as measured by western blotting. Cell death occurs via apoptosis in the presence of cyclosporin A, the permeability transition pore inhibitor, thus showing that permeability transition pore opening, not needed for cytochrome c release, is also unnecessary for apoptosis to occur.
Interaction between the vesicular glutamate transporter type 1 and endophilin A1, a protein essential for endocytosis
Authors: Vinatier Jacqueline , Herzog Etienne , Plamont Marie‐Aude , Wojcik Sonja M. , Schmidt Anne , Brose Nils , Daviet Laurent , El Mestikawy Salah , Giros Bruno 
Published: April 2006

AbstractIn the nerve terminal, neurotransmitter is actively packaged into synaptic vesicles before its release by Ca2+‐dependent exocytosis. The three vesicular glutamate transporters (VGLUT1, ‐2 and ‐3) are highly conserved proteins that display similar bioenergetic and pharmacological properties but are expressed in different brain areas. We used the divergent C‐terminus of VGLUT1 as a bait in a yeast two‐hybrid screen to identify and map the interaction between a proline‐rich domain of VGLUT1 and the Src homology domain 3 (SH3) domain of endophilin. We further confirmed this interaction by using different glutathione‐S‐transferase–endophilin fusion proteins to pull down VGLUT1 from rat brain extracts. The expression profiles of the two genes and proteins were compared on rat brain sections, showing that endophilin is most highly expressed in regions and cells expressing VGLUT1. Double immunofluorescence in the rat cerebellum shows that most VGLUT1‐positive terminals co‐express endophilin, whereas VGLUT2‐expressing terminals are often devoid of endophilin. However, neither VGLUT1 transport activity, endophilin enzymatic activity nor VGLUT1 synaptic targeting were altered by this interaction. Overall, the discovery of endophilin as a partner for VGLUT1 in nerve terminals strongly suggests the existence of functional differences between VGLUT1 and ‐2 terminals in their abilities to replenish vesicle pools.
Activation of 5‐lipoxygenase after oxygen‐glucose deprivation is partly mediated via NMDA receptor in rat cortical neurons
Authors: Ge Qiu‐Fu , Wei Er‐Qing , Zhang Wei‐Ping , Hu Xin , Huang Xiao‐Jia , Zhang Lei , Song Ying , Ma Zhen‐Qiu , Chen Zhong , Luo Jian‐Hong 
Published: April 2006

Abstract5‐Lipoxygenase (5‐LOX) is the enzyme metabolizing arachidonic acid to produce pro‐inflammatory leukotrienes. We have reported that 5‐LOX is translocated to the nuclear envelope after ischemic‐like injury in PC12 cells. In the present study, we determined whether 5‐LOX is activated (translocation and production of leukotrienes) after oxygen‐glucose deprivation (OGD) in primary rat cortical neurons; if so, whether this activation is mediated by NMDA receptor. After OGD, 5‐LOX was translocated to the nuclear envelope as detected by immunoblotting, immunostaining and green fluorescent protein‐5‐LOX transfection. 5‐LOX metabolites, cysteinyl‐leukotrienes (CysLTs) but not leukotriene B4, in the culture media were increased 0.5–1.5 h after recovery. Similarly, NMDA (100 µm) also induced 5‐LOX translocation, and increased the production of CysLTs during 0.5–1 h NMDA exposure. Both OGD and NMDA reduced neuron viability. NMDA receptor antagonist MK‐801 inhibited almost all the responses to OGD and NMDA; whereas 5‐LOX activating protein inhibitor MK‐886 and 5‐LOX inhibitor caffeic acid inhibited the reduction of neuron viability and the production of CysLTs, but did not affect 5‐LOX translocation. From these results, we conclude that OGD can activate 5‐LOX in primary rat cortical neurons, and that this activation may be partly mediated via activating NMDA receptor.
Expression and distribution of JNK/SAPK‐associated scaffold protein JSAP1 in developing and adult mouse brain
Authors: Miura Eriko , Fukaya Masahiro , Sato Tokiharu , Sugihara Kazushi , Asano Masahide , Yoshioka Katsuji , Watanabe Masahiko 
Published: April 2006

AbstractThe c‐Jun N‐terminal kinase (JNK) is one of the three major mitogen‐activated protein kinases (MAPKs) playing key roles in various cellular processes in response to both extracellular and intracellular stimuli. JNK/SAPK‐associated protein 1 (JSAP1 also referred to as JIP3) is a JNK‐associated scaffold that controls the specificity and efficiency of JNK signaling cascades. Here we studied its expression in mouse brains. JSAP1 mRNA was expressed in developing and adult brains, showing spatial patterns similar to JNK1–3 mRNAs. In embryos, JSAP1 immunolabeling was intense for progenitor cells in the ventricular zone throughout the brain and in the external granular layer of the cerebellum, and for neurons and glial cells differentiating in the mantle zone. In adults, JSAP1 was distributed in various neurons and Bergmann glia, with higher levels in striatal cholinergic interneurons, telencephalic parvalbumin‐positive interneurons and cerebellar Purkinje cells. In these neurons, JSAP1 was observed as tiny particulate staining in spines, dendrites, perikarya and axons, where it was often associated with the smooth endoplasmic reticulum (sER) and cell membrane. Immunoblots revealed enriched distribution in the microsomal fraction and cytosolic fraction. Therefore, the characteristic cellular expression and subcellular distribution of JSAP1 might be beneficial for cells to efficiently link external stimuli to the JNK MAPK pathway and other intracellular machineries.
Oligodendrocyte excitotoxicity determined by local glutamate accumulation and mitochondrial function
Authors: Deng Wenbin , Yue Qin , Rosenberg Paul A. , Volpe Joseph J. , Jensen Frances E. 
Published: April 2006

AbstractDeveloping oligodendrocytes (OL precursors, pre‐OLs) express α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) subtype glutamate receptors (AMPARs) and are highly vulnerable to hypoxic‐ischemic or oxygen‐glucose deprivation (OGD)‐induced excitotoxic injury, yet the mechanisms of injury remain unclear. Here we investigated the role of glutamate accumulation and mitochondrial function in OGD‐induced pre‐OL toxicity in vitro. Bulk glutamate concentration in the culture medium did not increase during OGD and OGD‐conditioned medium did not transfer toxicity to naïve cells. Facilitation of glutamate diffusion by constant agitation of the culture reduced, while inhibition of glutamate diffusion by increasing medium viscosity with dextran enhanced, OGD‐induced pre‐OL injury. Depletion of extracellular glutamate by the glutamate scavenging system, glutamate‐pyruvate transaminase plus pyruvate, attenuated pre‐OL injury during OGD. Together these data suggest that local glutamate accumulation is critical for OGD toxicity. Interestingly, under normoxic conditions, addition of glutamate to pre‐OLs did not cause receptor‐mediated toxicity, but the toxicity could be unmasked by mitochondrial impairment with mitochondrial toxins. Furthermore, OGD caused mitochondrial potential collapse that was independent of AMPAR activation, and OGD toxicity was enhanced by mitochondrial toxins. These data demonstrate that pre‐OL excitotoxicity is exacerbated by mitochondrial dysfunction during OGD. Overall, our results indicate that OGD‐induced pre‐OL injury is a novel form of excitotoxicity caused by the combination of local glutamate accumulation that occurs without an increase in bulk glutamate concentration and mitochondrial dysfunction. Therapeutic strategies targeting local glutamate concentration and mitochondrial injury during hypoxia‐ischemia may be relevant to human disorders associated with pre‐OL excitotoxicity.