bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serotonin 5‐HT2Creceptor protein expression is enriched in synaptosomal and post‐synaptic compartments of rat cortex
Authors: Anastasio Noelle C. , Lanfranco Maria Fe , Bubar Marcy J. , Seitz Patricia K. , Stutz Sonja J. , McGinnis Andrew G. , Watson Cheryl S. , Cunningham Kathryn A. 
Published: March 2010

J. Neurochem.(2010)113, 1504–1515.AbstractThe action of serotonin (5‐HT) at the 5‐HT2Creceptor (5‐HT2CR) in cerebral cortex is emerging as a candidate modulator of neural processes that mediate core phenotypic facets of several psychiatric and neurological disorders. However, our understanding of the neurobiology of the cortical 5‐HT2CR protein complex is currently limited. The goal of the present study was to explore the subcellular localization of the 5‐HT2CR in synaptosomes and the post‐synaptic density, an electron‐dense thickening specialized for post‐synaptic signaling and neuronal plasticity. Utilizing multiples tissues (brain, peripheral tissues), protein fractions (synaptosomal, post‐synaptic density), and controls (peptide neutralization, 5‐HT2CR stably‐expressing cells), we established the selectivity of two commercially available 5‐HT2CR antibodies and employed the antibodies in western blot and immunoprecipitation studies of prefrontal cortex (PFC) and motor cortex, two regions implicated in cognitive, emotional and motor dysfunction. For the first time, we demonstrated the expression of the 5‐HT2CR in post‐synaptic density‐enriched fractions from both PFC and motor cortex. Co‐immunoprecipitation studies revealed the presence of post‐synaptic density‐95 within the 5‐HT2CR protein complex expressed in PFC and motor cortex. Taken together, these data support the hypothesis that the 5‐HT2CR is localized within the post‐synaptic thickening of synapses and is therefore positioned to directly modulate synaptic plasticity in cortical neurons.
Non‐classical exocytosis of α‐synuclein is sensitive to folding states and promoted under stress conditions
Authors: Jang Ara , Lee He‐Jin , Suk Ji‐Eun , Jung Jin‐Woo , Kim Kwang‐Pyo , Lee Seung‐Jae 
Published: March 2010

J. Neurochem. (2010) 113, 1263–1274.AbstractParkinson’s disease is characterized by deposition of misfolded/aggregated α‐synuclein proteins in multiple regions of the brain. Neurons can release α‐synuclein; through this release, pathological forms of α‐synuclein are propagated between neurons, and also cause neuroinflammation. In this study, we demonstrate that release of α‐synuclein is consistently increased under various protein misfolding stress conditions in both neuroblastoma and primary neuron models. This release is mediated by a non‐classical, endoplasmic reticulum (ER)/Golgi‐independent exocytosis, and stress‐induced release coincides with increased translocation of α‐synuclein into vesicles. Both vesicle translocation and secretion were blocked by attachment of a highly stable, globular protein to α‐synuclein, whereas forced protein misfolding resulted in an increase in both of these activities. Mass spectrometry analysis showed a higher degree of oxidative modification in secreted α‐synuclein than in the cellular protein. Together, these results suggest that structurally abnormal, damaged α‐synuclein proteins translocate preferentially into vesicles and are released from neuronal cells via exocytosis.
Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAAreceptor expression, and behavioral sensitivity to anxiolytic drugs
Authors: Calza Arianna , Sogliano Cristiana , Santoru Francesca , Marra Carla , Angioni Maria Maddalena , Mostallino Maria Cristina , Biggio Giovanni , Concas Alessandra 
Published: March 2010

J. Neurochem.(2010)113, 1285–1295.AbstractGonadal steroids, in particular estradiol, exert important actions during pre‐ and perinatal periods in the regulation of sexual dimorphism and development of the nervous system. We have now examined the effects of neonatal estradiol administration in female rats on brain concentrations of the neuroactive steroids allopregnanolone and tetrahydrodeoxycorticosterone, expression of GABAAreceptor subunits, and behavioral sensitivity to benzodiazepines and allopregnanolone. Administration of β‐estradiol 3‐benzoate on the day of birth resulted in marked decreases in the concentrations of progesterone and allopregnanolone in the cerebral cortex at 21, 60, and 180 days after birth. The concentrations of tetrahydrodeoxycorticosterone, 17β‐estradiol, and dehydroepiandrosterone in the brain at 60 days were not affected by such treatment. Neonatal administration of β‐estradiol 3‐benzoate also increased the cerebrocortical abundance of α1, α2, and γ2subunits of the GABAAreceptor without affecting that of α3, α4, α5, or δ subunits. Diazepam induced a greater reduction in locomotor activity as well as a more pronounced anxiolytic‐like effect in the elevated plus‐maze test in rats subjected to neonatal treatment with β‐estradiol 3‐benzoate than in vehicle‐treated controls, while allopregnanolone induced a similar effect in both groups. These effects of estradiol suggest that it plays a major role in regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system.
Molecular genetic approaches to understanding the roles and regulation of iron in brain health and disease
Authors: Johnstone Daniel , Milward Elizabeth A. 
Published: March 2010

J. Neurochem. (2010) 113, 1369–1386.AbstractIron is essential in the brain, yet too much iron can be toxic. Tight regulation of iron in the brain may involve intrinsic mechanisms that control internal homeostasis independent of systemic iron status. Iron abnormalities occur in various neurological disorders, usually with symptoms or neuropathology associated with movement impairment or behavioral disturbances rather than cognitive impairment or dementia. Consistent with this, polymorphisms in the HFE gene, associated with the iron overload disorder hemochromatosis, show stronger associations with the movement disorder amyotrophic lateral sclerosis (motor neuron disease) than with cognitive impairment. Such associations may arise because certain brain regions involved in movement or executive control are particularly iron‐rich, notably the basal ganglia, and may be highly reliant on iron. Various mechanisms, including iron redistribution causing functional iron deficiency, lysosomal and mitochondrial abnormalities or oxidative damage, could underlie iron‐related neuropathogenesis. Clarifying how iron contributes causatively to neurodegeneration may improve treatment options in a range of neurodegenerative disorders. This review considers how modern molecular genetic approaches can be applied to resolve the complex molecular systems and pathways by which brain iron homeostasis is regulated and the molecular changes that occur with iron dyshomeostasis and neuropathogenesis.
CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamine N‐acetyltransferase mRNA in chicken cone photoreceptors
Authors: Haque Rashidul , Ali Fatima G. , Biscoglia Rebecca , Abey Jane , Weller Joan , Klein David , Iuvone P. Michael 
Published: March 2010

J. Neurochem. (2010) 113, 1296–1306.AbstractCircadian clocks in vertebrates are thought to be composed of transcriptional‐translational feedback loops involving a highly conversed set of ‘clock genes’ namely, period (Per1‐3) and cryptochrome (Cry1‐2), which encode negative transcriptional regulators; and Bmal1, Clock, and Npas2, which encode positive regulators. Aanat, which encodes arylalkylamine N‐acetyltransferase (AANAT), the key regulatory enzyme that drives the circadian rhythm of melatonin synthesis, contains a circadian E‐box element (CACGTG) in its proximal promoter that is potentially capable of binding CLOCK : BMAL1 and NPAS2 : BMAL1 heterodimers. The present study was conducted to investigate whether CLOCK and/or NPAS2 regulates Aanat expression in photoreceptor cells. Npas2 and Clock are both expressed in photoreceptor cells in vivo and in vitro. To assess the roles of CLOCK and NPAS2 in Aanat expression, gene‐specific micro RNA vectors were used to knock down expression of these clock genes in photoreceptor‐enriched cell cultures. The knockdown of CLOCK protein significantly reduced the circadian expression of Npas2, Per2, and Aanat transcripts but had no effect on the circadian rhythm of Bmal1 transcript level. The knockdown of NPAS2 significantly damped the circadian rhythm of Aanat mRNAs but had no effect on circadian expression of any of clock genes examined, except Npas2 itself. Chromatin immunoprecipitation studies indicated that both CLOCK and NPAS2 bound to the Aanat promoter in situ. Thus, CLOCK and NPAS2 have overlapping roles in the clock output pathway that regulates the rhythmic expression of Aanat in photoreceptors. However, CLOCK plays the predominant role in the chicken photoreceptor circadian clockwork mechanism, including the regulation of NPAS2 expression.
Insulin‐like growth factor binding protein‐1 activates integrin‐mediated intracellular signaling and migration in oligodendrocytes
Authors: Chesik Daniel , De Keyser Jacques , Bron Reinier , Fuhler Gwenny M. 
Published: March 2010

J. Neurochem. (2010) 113, 1319–1330.AbstractIn multiple sclerosis (MS), oligodendrocytes in lesions are lost, leaving damaged tissue virtually devoid of these myelin‐producing cells. Our group has recently demonstrated enhanced expression of insulin‐like growth factor (IGF) binding protein‐1 (IGFBP‐1) in oligodendrocytes (CNPase+) localized adjacent to MS lesions. In the present study, we demonstrate IGF‐1‐independent actions of IGFBP‐1 on OLN‐93 oligodendroglial cells, including activation of kinases ERK1/2, focal adhesion kinase and p21‐activated kinase as well as small monomeric GTPases Rac and Ral. Activation of these intracellular signaling components was inhibited by GRGDS peptide, indicating signaling through integrin receptors. While both IGF‐1 and IGFBP‐1 demonstrated rapid induction of actin polymerization, IGFBP‐1 proved to be a more potent inducer of migration than IGF‐1, inducing a threefold increased migration rate. Furthermore, through integrin receptor signaling IGFBP‐1 induced rapid transient translocalization of intracellular Rac toward punctuated structures followed by translocation of Rac to the plasma membrane. Our results suggest that up‐regulation of IGFBP‐1 in oligodendrocytes in MS may serve two functions: (i) regulate IGF‐1 actions, (ii) exert IGF‐independent effects through its RGD sequence.
Amphotericin B, identified from a natural product screen, antagonizes CNS inhibitors to promote axon growth via activation of an Akt pathway in neurons
Authors: Gao Ying , Deng Kangwen , Cao Zixuan , Graziani Edmund I. , Gilbert Adam M. , Koehn Frank E. , Wood Andrew , Doherty Patrick , Walsh Frank S. 
Published: March 2010

J. Neurochem. (2010) 113, 1331–1342.AbstractOne of the major barriers to successful axon regeneration in the adult CNS is the presence of inhibitory molecules that originate from the myelin sheath and glial scar. So far, only a small number of pharmacological compounds have exhibited functional activity against CNS inhibitors in promoting axon regeneration after injury. To search for novel compounds that enhance neurite outgrowth in vitro, we initiated a screen of a collection of natural products. We identified four compounds with the potential to promote growth over a myelin substrate. Of these, Amphotericin B (AmB) was shown to enhance neurite outgrowth and antagonize activities of major myelin associated inhibitors and glial‐scar‐derived chondroitin sulfate proteoglycans. AmB was found to activate Akt and thereby suppress the activity of glycogen synthase kinase 3 beta. Also, a cell permeable peptide that inhibits Akt activity was shown to block the effect of AmB in promoting axonal growth, while another peptide that increases Akt activity stimulated axonal growth in the presence of the myelin associated inhibitors. Our results suggest that AmB can promote neurite outgrowth over a wide range of inhibitory substrates via a mechanism that involves activation of Akt.
Role of the c‐Jun N‐terminal kinase pathway in retinal excitotoxicity, and neuroprotection by its inhibition
Authors: Bessero Anne‐Caroline , Chiodini Florence , Rungger‐Brändle Elisabeth , Bonny Christophe , Clarke Peter G. H. 
Published: March 2010

J. Neurochem. (2010) 113, 1307–1318.AbstractRetinal excitotoxicity is associated with retinal ischemia, and with glaucomatous and traumatic optic neuropathy. The present study investigates the role of c‐Jun N‐terminal kinase (JNK) activation in NMDA‐mediated retinal excitotoxicity and determines whether neuroprotection can be obtained with the JNK pathway inhibitor, d‐form of JNK‐inhibitor 1 (d‐JNKI‐1). Young adult rats received intravitreal injections of 20 nmol NMDA, which caused extensive neuronal death in the inner nuclear and ganglion cell layers. This excitotoxicity was associated with strong activation of calpain, as revealed by fodrin cleavage, and of JNK. The cell‐permeable peptide d‐JNKI‐1 was used to inhibit JNK. Within 40 min of its intravitreal injection, FITC‐labeled d‐JNKI‐1 spread through the retinal ganglion cell layer into the inner nuclear layer and interfered with the NMDA‐induced phosphorylation of JNK. Injections of unlabeled d‐JNKI‐1 gave unprecedentedly strong neuroprotection against cell death in both layers, lasting for at least 10 days. The NMDA‐induced calpain‐specific fodrin cleavage was likewise strongly inhibited by d‐JNKI‐1. Moreover the electroretinogram was partially preserved by d‐JNKI‐1. Thus, the JNK pathway is involved in NMDA‐mediated retinal excitotoxicity and JNK inhibition by d‐JNKI‐1 provides strong neuroprotection as shown morphologically, biochemically and physiologically.
An evolutionary fast‐track to biocalcification
Authors: JACKSON D. J. , THIEL V. , WÖRHEIDE G. 
Published: March 2010

AbstractThe ability to construct mineralized shells, spicules, spines and skeletons is thought to be a key factor that fuelled the expansion of multicellular animal life during the early Cambrian. The genes and molecular mechanisms that control the process of biomineralization in disparate phyla are gradually being revealed, and it is broadly recognized that an insoluble matrix of proteins, carbohydrates and other organic molecules are required for the initiation, regulation and inhibition of crystal growth. Here, we show that Astrosclera willeyana, a living representative of the now largely extinct stromatoporid sponges (a polyphyletic grade of poriferan bauplan), has apparently bypassed the requirement to evolve many of these mineral‐regulating matrix proteins by using the degraded remains of bacteria to seed CaCO3 crystal growth. Because stromatoporid sponges formed extensive reefs during the Paelozoic and Mesozoic eras (fulfilling the role that stony corals play in modern coral reefs), and fossil evidence suggests that the same process of bacterial skeleton formation occurred in these stromatoporid ancestors, we infer that some ancient reef ecosystems might have been founded on this microbial–metazoan relationship.
α1‐ and α2‐Adrenoceptor hyporesponsiveness in isolated bisected vas deferens of bile duct‐ligated rats
Authors: Heydari F. , Mehr S. E. , Samini M. 
Published: March 2010

Summary1 It has been suggested that cholestasis accompanied with changes in autonomic balance and hyporesponsiveness in muscarinic and adrenergic receptors of some organs, e.g. cardiovascular system. Increased plasma levels of epinephrine and norepinephrine has been shown during cholestasis suggesting augmented activity of sympathetic nervous system. In this study we evaluate both α1and α2responsiveness in isolated rat vas deferens, as a tissue with rich adrenergic innervations.2 Epididymal and prostatic halves of vas deferens responsiveness have been studied to phenylephrine and clonidine respectively in three groups of un‐operated, sham‐operated (sham), and bile duct‐ligated (BDL) rats.3 Our results indicate that in vas deferens of BDL animals, the concentration‐response curve of both phenylephrine and clonidine shifted to rightward compared to control group, while the position of concentration‐response curve of sham group did not change significantly (P > 0.05). EC50of phenylephrine and IC50of clonidine were increased showing a decreased responsiveness of tissue to phenylephrine (P < 0.05) and clonidine (P < 0.001) in BDL rats.4 In this study, both subtype of α‐adrenoceptors (α1and α2) has been studied in cholestatic rat vas deference. Our results showed that cholestasis induce hyporesponsiveness to phenylephrine and clonidine. These results are consistent with previous reports, suggesting the hyporesponsiveness of α1‐adrenoceptors in pulmonary artery and papillary muscle and mesenteric beds. Our conclusion is that the cholestasis induces hyporesponsiveness to phenylephrine and clonidine in epididymal (α1‐adrenoceptors) and prostatic (α2‐adrenoceptors) halves of rat vas deferens respectively. Although the logical explanation to this hyporesponsiveness is the down regulation but it has been suggested that it is not because of down regulation.
Comparison of Tibial Plateau Angle Changes after Tibial Plateau Leveling Osteotomy Fixation with Conventional or Locking Screw Technology
Authors: Conkling Amanda L. , Fagin Bennett , Daye R. Mark 
Published: March 2010

Objective: To compare the effects of locking and conventional screws on postoperative tibial plateau angle (TPA), osteotomy healing, and complication rate after tibial plateau leveling osteotomy (TPLO) in dogs treated for naturally occurring cranial cruciate ligament (CCL) rupture.Study Design: Prospective clinical study.Study Population: Dogs (n=118) with CCL rupture.Methods:Dogs (≥20 kg) with unilateral CCL rupture and sufficient bone stock for TPLO and use of a 3.5‐mm‐broad or ‐narrow TPLO plate were sequentially allocated to have plate fixation with locking or conventional screws. Data analyzed included breed, age, sex, body weight, body condition score, limb operated, implants used, meniscal status, operative time, and days to recheck. Preoperative, immediate postoperative, and 8‐week recheck mediolateral radiographs were reviewed, and TPA, complications, and healing status were evaluated.Results: Stifles in the locking screw group had significantly less change in postoperative TPA than stifles in the conventional screw group. Locking screw fixation also had significantly higher grades of osteotomy healing, assessed on a mediolateral radiographic view.Conclusions: TPLO plates secured with locking screws are acceptable when compared with those secured with conventional screws; osteotomy healing is improved and TPA better conserved when using locking screws.Clinical Relevance: Locking screw fixation serves to increase stabilization of TPA during TPLO healing and provides improved radiographic evidence of osteotomy healing.
Predictive Variables for Complications after TPLO with Stifle Inspection by Arthrotomy in 1000 Consecutive Dogs
Authors: Fitzpatrick Noel , Solano Miguel Angel 
Published: March 2010

Objective:To evaluate risk factors for complications, including meniscal injury and infection, after tibial plateau leveling osteotomy (TPLO) in dogs.Study Design:Retrospective case series.Sample Population:Dogs (n=1000; 1146 stifles) with cranial cruciate ligament (CCL) rupture that had TPLO.Methods:Medical records (January 2004–March 2009) were reviewed for dogs operated sequentially by medial arthrotomy with instrumented meniscal inspection (IMI) and TPLO by a single experienced surgeon. Multiple logistic regression models were used to evaluate independent contribution of risk factors to the recorded complications.Results:Overall complication rate was 14.8%, of which 6.6% were major complications. Incidence of primary meniscal injury (PMI) was 33.2%, and subsequent meniscal injury (SMI) 2.8%. Postoperative infection occurred in 6.6% dogs. Bilateral CCL rupture was diagnosed in 14.6% dogs and no statistically significant complication incidence difference was recorded for simultaneous or staged bilateral surgical procedures. Administration of postoperative antibacterial therapy and being a Labrador reduced infection incidence, whereas increased body‐weight and being an intact male increased infection risk. Increased body‐weight and complete (versus partial) CCL rupture were significant predictors of overall complications.Conclusions:Incidence of SMI recorded in this study is similar to that reported previously involving arthroscopic meniscal inspection at time of TPLO. Infection was the single most important complication and antibiotic therapy was protective. Complication rate did not differ between bilateral simultaneous or staged procedures.Clinical Relevance:Complication rate after TPLO with arthrotomy and IMI is lower than previously reported, bilateral simultaneous TPLO is reasonable, and incidence of major complications compares favorably with general orthopedic procedures.
Effect of Tibial Plateau Leveling Osteotomy on Patellar Tendon Angle: A Radiographic Cadaveric Study
Authors: Drygas Kevin A. , Pozzi Antonio , Goring Robert L. , Horodyski MaryBeth , Lewis Daniel D. 
Published: March 2010

Objectives: To determine the effect of tibial plateau leveling osteotomy (TPLO) on patellar tendon angle (PTA) in dogs.Study Design: Cadaveric radiographic study.Animals: Pelvic limb pairs (n=5) obtained from skeletally mature dogs, weighing 22–36 kg.Methods: TPLO was performed using a radiolucent jig that allowed for plateau segment rotation to a tibial plateau angle (TPA) of 15°, 6°, and 0°. Before, and at each of the prescribed rotations, PTA was measured by the tibial plateau (PTATP) and common tangent (PTACT) methods with the stifle positioned at 135° of flexion. Linear regression analysis was performed to evaluate the correlation between TPA and PTA.Results: At a mean (±SD) TPA of 5.9±0.7°, mean±SD PTATP and PTACT were 94.1±1.6° and 86.8±2.5°, respectively. A linear correlation was observed between TPA and PTATP (r=0.85) and between TPA and PTACT (r=0.61). Based on the regression equation of TPA and PTACT, a TPA of 12° corresponded to a PTACT of ∼90°.Conclusion: TPLO to a TPA of 6° reduces PTA to values similar to those recommended when performing tibial tuberosity advancement in dogs with cranial cruciate ligament insufficiency.Clinical Relevance: TPLO may neutralize tibial thrust by modifying PTA as well as decreasing TPA. TPLO to a TPA of 6° may not be necessary to neutralize the cranial tibial thrust according to the plateau rotation based on PTACT measurement.