bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of cortical connections
Authors: Price David J. , Kennedy Henry , Dehay Colette , Zhou Libing , Mercier Marjorie , Jossin Yves , Goffinet André M. , Tissir Fadel , Blakey Daniel , Molnár Zoltán 
Published: March 2006

AbstractThe cortex receives its major sensory input from the thalamus via thalamocortical axons, and cortical neurons are interconnected in complex networks by corticocortical and callosal axons. Our understanding of the mechanisms generating the circuitry that confers functional properties on cortical neurons and networks, although poor, has been advanced significantly by recent research on the molecular mechanisms of thalamocortical axonal guidance and ordering. Here we review recent advances in knowledge of how thalamocortical axons are guided and how they maintain order during that process. Several studies have shown the importance in this process of guidance molecules including Eph receptors and ephrins, members of the Wnt signalling pathway and members of a novel planar cell polarity pathway. Signalling molecules and transcription factors expressed with graded concentrations across the cortex are important in establishing cortical maps of the topography of sensory surfaces. Neural activity, both spontaneous and evoked, plays a role in refining thalamocortical connections but recent work has indicated that neural activity is less important than was previously thought for the development of some early maps. A strategy used widely in the development of corticocortical and callosal connections is the early overproduction of projections followed by selection after contact with the target structure. Here we discuss recent work in primates indicating that elimination of juvenile projections is not a major mechanism in the development of pathways feeding information forward to higher levels of cortical processing, although its use is common to developing feedback pathways.
Endogenous opioids upregulate brain‐derived neurotrophic factor mRNA through δ‐ and µ‐opioid receptors independent of antidepressant‐like effects
Authors: Zhang Huina , Torregrossa Mary M. , Jutkiewicz Emily M. , Shi Yong‐Gong , Rice Kenner C. , Woods James H. , Watson Stanley J. , Holden Ko M. C. 
Published: March 2006

AbstractSystemic administration of δ‐opioid receptor (DOR) agonists decreases immobility in the forced swim test (FST) and increases brain‐derived neurotrophic factor (BDNF) mRNA expression in rats, indicating that DOR agonists may have antidepressant‐like effects. The aim of this study was to investigate the effects of central administration of endogenous opioid peptides on behavior in the FST and on brain BDNF mRNA expression in rats. Effects of endogenous opioids were compared with those produced by intracerebroventricular administration of a selective non‐peptidic DOR agonist (+)BW373U86. Antidepressant‐like effects were measured by decreased immobility in the FST. BDNF mRNA expression was determined by in situ hybridization. Centrally administered (+)BW373U86 decreased immobility and increased BDNF mRNA expression in the frontal cortex through a DOR‐mediated mechanism, because these effects were blocked by the DOR antagonist naltrindole, but not by the µ‐opioid receptor (MOR) antagonist naltrexone (NTX) or the κ‐opioid receptor antagonist nor‐binaltorphimine. Of all the endogenous opioids tested, only leu‐ and met‐enkephalin produced behavioral effects like those of (+)BW373U86 in the FST. Unlike (+)BW373U86, the enkephalins upregulated BDNF mRNA expression in the hippocampus through DOR‐ and MOR‐mediated mechanisms. β‐Endorphin, endomorphin‐1 and endomorphin‐2 significantly increased BDNF mRNA levels in the frontal cortex, hippocampus and amygdala without reducing immobility; and most of these effects were reversed by NTX. This study is the first to provide evidence that endogenous opioids can upregulate BDNF mRNA expression through the DOR and MOR, and that leu‐ and met‐enkephalin have similar pharmacological profiles to synthetic DOR agonists in producing antidepressant‐like effects.
Dopamine desynchronizes the pace‐making neuronal activity of rat respiratory rhythm generation
Authors: Fujii Morimitsu , Umezawa Kazuo , Arata Akiko 
Published: March 2006

AbstractIn an excised Wistar rat medulla‐spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D4 receptors [Fujii et al., (2004)Neurosci. Res., 50, 355–359.] In the present paper, we investigated the effect of dopamine on pre‐inspiratory (Pre‐I) and inspiratory (I) neurons using the combination of an optical recording technique with a voltage‐sensitive dye, unit recording and patch‐clamp recording. Optical imaging of the ventral surface of the block preparation disclosed different locations and activity patterns of Pre‐I and I neurons. In addition to slowing the rhythm, dopamine depressed respiratory activity of Pre‐I neurons collectively but not that of I neurons. The dopaminergic suppression of Pre‐I neurons was mimicked by a dopamine D4 receptor agonist, PD168077. Unit recording and patch‐clamp recording demonstrated that dopamine depolarizes Pre‐I neurons, disperses Pre‐I firing and depresses Pre‐I phase postsynaptic potentials (PSPs) of I neurons. Immunohistological investigation revealed that Pre‐I neurons express dopamine D4 receptors. We found that approximately 60% of Pre‐I neurons express dopamine D4 receptors. These results show that dopaminergic respiratory rhythm depression is due to dispersion of synchronized Pre‐I driving of I neurons caused by dopamine D4 receptor stimulation of Pre‐I neurons.
The opioid peptide nociceptin/orphanin FQ mediates prostaglandin E2‐induced allodynia, tactile pain associated with nerve injury
Authors: Okuda‐Ashitaka Emiko , Minami Toshiaki , Matsumura Shinji , Takeshima Hiroshi , Reinscheid Rainer K. , Civelli Olivier , Ito Seiji 
Published: March 2006

AbstractPain often outlasts its usefulness as warning and aid in wound healing, and becomes chronic and intractable after tissue damage and nerve injury. Many molecules have been implicated as mediators and modulators in persistent pain such as hyperalgesia and tactile pain (allodynia). We previously showed that prostaglandin (PG) E2, PGF2αor the neuropeptide nociceptin, also called orphanin FQ (N/OFQ) administered intrathecally (i.t.) produced allodynia in conscious mice. In the present study, we examined the relationship of pain responses between PGs and N/OFQ using the N/OFQ receptor (NOP) antagonist,N‐(4‐amino‐2‐methylquinolin‐6‐yl)‐2‐(4‐ethylphenoxy‐methyl)benzamide monohydrochloride (JTC‐801), and in mice lacking the N/OFQ prepropeptide (ppN/OFQ–/–) and the NOP receptor (NOP–/–). JTC‐801 dose‐dependently blocked the N/OFQ‐ and PGE2‐induced allodynia, but not the PGF2α‐induced one. Neither N/OFQ nor PGE2induced allodynia in NOP–/–mice. By contrast, the N/OFQ‐induced allodynia was not affected by inhibition of PG production by a 60‐min pretreatment with the non‐steroidal anti‐inflammatory drug, indomethacin. Among PGE receptor (EP) subtype‐selective agonists, the EP4 agonist, AE1‐329, markedly stimulated the release of N/OFQ from spinal slices and induced allodynia. AE1‐329 also increased nitric oxide production in spinal slices using fluorescent nitric oxide detection, which was blocked by pretreatment with JTC‐801. Conversely, PGE2‐induced allodynia was not observed in ppN/OFQ–/–mice. N/OFQ immunoreactive puncta were colocalized with EP4. Taken together, these results demonstrate that PGE2induced allodynia by stimulation of N/OFQ release in the spinal cord via EP4 receptor subtypes.
Molecular mechanisms of cortical differentiation
Authors: Guillemot Francois , Molnár Zoltán , Tarabykin Victor , Stoykova Anastassia 
Published: March 2006

AbstractDuring development, several populations of progenitor cells in the dorsal telencephalon generate a large variety of neurons which acquire distinct morphologies and physiological properties and serve distinct functions in the mammalian cortex. This paper reviews recent work that has identified (i) key molecules involved in the specification and differentiation of cortical neurons, (ii) novel genes which distinguish distinct subsets of cortical progenitors and may be involved in the diversification of cortical neurons present in different cortical layers, and (iii) mechanisms involved in the generation of different projection neuronal subtypes in the well‐studied model of layer 5 of the rodent cortex.
Circulating insulin‐like growth factor I and functional recovery from spinal cord injury under enriched housing conditions
Authors: Koopmans Guido C. , Brans Maike , Gómez‐Pinilla Fernando , Duis Simone , Gispen Willem Hendrick , Torres‐Aleman Ignazio , Joosten Elbert A. J. , Hamers Frank P. T. 
Published: March 2006

AbstractVoluntary locomotor training as induced by enriched housing of rats stimulates recovery of locomotion after spinal cord injury (SCI). Generally it is thought that spinal neural networks of motor‐ and interneurons located in the ventral and intermediate laminae within the lumbar intumescence of the spinal cord, also referred to as central pattern generators (CPGs), are the ‘producers of locomotion’ and play a pivotal role in the amelioration of locomotor deficits after SCI. It has been suggested that locomotor training provides locomotor‐specific sensory feedback into the CPGs, which stimulates remodeling of central nervous system pathways, including motor systems. Several molecules have been proposed to potentiate this process but the underlying mechanisms are not yet known. To understand these mechanisms, we studied the role of insulin‐like growth factor (IGF) I in functional recovery from SCI under normal and enriched environment (EE) housing conditions. In a first experiment, we discovered that subcutaneous administration of IGF‐I resulted in better locomotor recovery following SCI. In a second experiment, detailed analysis of the observed functional recovery induced by EE revealed full recovery of hindlimb coordination and stability of gait. This EE‐dependent functional recovery was attenuated by alterations in the pre‐synaptic bouton density within the ventral gray matter of the lumbar intumescence or CPG area. Neutralization of circulating IGF‐I significantly blocked the effectiveness of EE housing on functional recovery and diminished the EE‐induced alterations in pre‐synaptic bouton density within the CPG area. These results support the use of IGF‐I as a possible therapeutic aid in early rehabilitation after SCI.
CXCL10‐induced cell death in neurons: role of calcium dysregulation
Authors: Sui Yongjun , Stehno‐Bittel Lisa , Li Shanping , Loganathan Rajprasad , Dhillon Navneet K. , Pinson David , Nath Avindra , Kolson Dennis , Narayan Opendra , Buch Shilpa 
Published: March 2006

AbstractChemokines play a key role in the regulation of central nervous system disease. CXCL10 over‐expression has been observed in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease and HIV‐associated dementia. More recent studies by others and us have shown that CXCL10 elicits apoptosis in fetal neurons. The mechanism of CXCL10‐mediated neurotoxicity, however, remains unclear. In this study, we provide evidence for the direct role of Ca2+ dysregulation in CXCL10‐mediated apoptosis. We demonstrate that treatment of fetal neuronal cultures with exogenous CXCL10 produced elevations in intracellular Ca2+ and that this effect was modulated via the binding of CXCL10 to its cognate receptor, CXCR3. We further explored the association of intracellular Ca2+ elevations with the caspases that are involved in CXC10‐induced neuronal apoptosis. Our data showed that increased Ca2+, which is available for uptake by the mitochondria, is associated with membrane permeabilization and cytochrome c release from this compartment. The released cytochrome c then activates the initiator active caspase‐9. This initiator caspase sequentially activates the effector caspase‐3, ultimately leading to apoptosis. This study identifies the temporal signaling cascade involved in CXCL10‐mediated neuronal apoptosis and provides putative targets for pharmaceutical intervention of neurological disorders associated with CXCL10 up‐regulation.
Diurnal regulation of the gastrin‐releasing peptide receptor in the mouse circadian clock
Authors: Karatsoreos Ilia N. , Romeo Russell D. , McEwen Bruce S. , Silver Rae 
Published: March 2006

AbstractIn mammals, circadian rhythms are generated by the suprachiasmatic nuclei (SCN) of the hypothalamus. SCN neurons are heterogeneous and can be classified according to their function, anatomical connections, morphology and/or peptidergic identity. We focus here on gastrin‐releasing peptide‐ (GRP) and on GRP receptor‐ (GRPr) expressing cells of the SCN. Pharmacological application of GRP in vivo or in vitro can shift the phase of circadian rhythms, and GRPr‐deficient mice show blunted photic phase shifting. Given the in vivo and in vitro effects of GRP on circadian behavior and on SCN neuronal activity, we investigated whether the GRPr might be under circadian and/or diurnal control. Using in situ hybridization and autoradiographic receptor binding, we localized the GRPr in the mouse SCN and determined that GRP binding varies with time of day in animals housed in a light–dark cycle but not in conditions of constant darkness. The latter results were confirmed with Western blots of SCN tissue. Together, the present findings reveal that changes in GRPr are light driven and not endogenously organized. Diurnal variation in GRPr activity probably underlies intra‐SCN signaling important for entrainment and phase shifting.
Rpe65 as a modifier gene for inherited retinal degeneration
Authors: Samardzija M. , Wenzel A. , Naash M. , Remé C. E. , Grimm C. 
Published: March 2006

AbstractLight accelerates progression of retinal degeneration in many animal models of retinitis pigmentosa (RP). A sequence variant in the Rpe65 gene (Rpe65450Leu or Rpe65450Met) can act as a modulator of light‐damage susceptibility in mice by influencing the kinetics of rhodopsin regeneration and thus by modulating the photon absorption. Depending on exposure duration and light intensity applied, white fluorescent light induces photoreceptor apoptosis and retinal degeneration in wild‐type mice by the activation of one of two known molecular pathways. These pathways depend, respectively, on activation of the transcription factor c‐Fos/AP‐1 and on phototransduction activity. Here we tested Rpe65 as a genetic modifier for inherited retinal degeneration and analysed which degenerative pathway is activated in a transgenic mouse model of autosomal dominant RP. We show that retinal degeneration was reduced in mice expressing the Rpe65450Met variant and that these mice retained more visual pigment rhodopsin than did transgenic mice expressing the Rpe65450Leu variant. In addition, lack of phototransduction slowed retinal degeneration whereas ablation of c‐Fos had no effect. We conclude that sequence variations in the Rpe65 gene can act as genetic modifiers in inherited retinal degeneration, presumably by regulating the daily rate of photon absorption through the modulation of rhodopsin regeneration kinetics. Increased absorption of photons and/or light sensitivity appear to accelerate retinal degeneration via an apoptotic cascade which involves phototransduction but not c‐Fos.
Familiar and environmental factors influencing atopic dermatitis in the childhood
Authors: Sebõk B , Schneider I ,   Primary Care Paediatricians in Baranya County, Harangi F 
Published: March 2006

AbstractBackground  The increase in the incidence of atopic dermatitis (AD) in developed countries has been related to familiar and environmental factors. This survey was undertaken to investigate the family background, birthweight and the home environment of children suffering from AD in order to point out the possible factors that provoke the development of the disease.Methods  The study uses data collected by means of self‐administered questionnaires and discusses 461 cases of children (age 0–12) with active skin signs of AD. The control group comprised of 343 children (age 0–12) with no skin signs or positive lifetime history of AD. Associations between familiar and various home environmental factors and the risk of AD were calculated by means of odds ratios.Results  There were statistically significant positive associations between atopic eczema symptoms and higher birthweight, small households, wall‐to‐wall carpets, as well as indoor‐kept pets. Day‐nursery attendance, heating system and indoor smoking, however, did not significantly alter the risk of the disease.Conclusions  Because of the limitations of a retrospective questionnaire study, further research is needed to confirm these associations and clarify whether they are causative.
β‐Amyloid protein converting enzyme 1 and brain‐specific type II membrane protein BRI3: binding partners processed by furin
Authors: Wickham Louise , Benjannet Suzanne , Marcinkiewicz Edwige , Chretien Michel , Seidah Nabil G. 
Published: March 2006

AbstractUsing a yeast two‐hybrid system, we screened a human brain cDNA library for possible interacting proteins with the C‐terminal cytosolic tail of the β‐secretase β‐amyloid protein converting enzyme (BACE)1. This identified seven potential candidates, including the brain‐specific type II membrane protein BRI3. Co‐localization and co‐immunoprecipitation experiments confirmed that BACE1 and BRI3 co‐localize and interact with each other via the cytosolic tail of BACE1. Furthermore, pulse and pulse‐chase analyses revealed that the pro‐protein convertases furin, and to a lesser extent PC7 and PC5A, process BRI3 into a C‐terminal secreted ∼ 4‐kDa product. Thus, furin efficiently processes both pro‐BACE1 and its novel interacting protein pro‐BRI3.
Effect of a Dementia Care Management Intervention on Primary Care Provider Knowledge, Attitudes, and Perceptions of Quality of Care
Authors: Chodosh Joshua , Berry Elise , Lee Martin , Connor Karen , DeMonte Robert , Ganiats Theodore , Heikoff Lisa , Rubenstein Laurence , Mittman Brian , Vickrey Barbara 
Published: March 2006

OBJECTIVES: To evaluate the effect of a multicomponent dementia care management program on primary care provider knowledge, attitudes, and perceptions of quality of dementia care.DESIGN: A clinic‐level randomized, controlled trial of a comprehensive care management program for patients with dementia and their nonprofessional caregivers. The program included provider education and protocols for care managers to communicate with patients' medical providers.SETTING: Sixteen clinics (eight intervention, eight usual care) in three healthcare systems in San Diego, California.PARTICIPANTS: Two hundred thirty‐two medical providers; 129 from eight intervention clinics; 103 from eight usual‐care clinics.MEASUREMENTS: Providers were surveyed 9 months after intervention onset on knowledge (five items on four topics), attitudes about dementia (three items), and perception of quality of dementia care in their practice setting (three items). Multivariable linear and logistic regression models were used to evaluate the differences between intervention and usual‐care providers, adjusting for covariate effects across groups and clustering by clinic.RESULTS: One hundred sixty‐six of 232 (72%) providers responded. Intervention providers had better knowledge about assessing decision‐making capacity than usual‐care providers (adjusted difference in percentage correct=12%; adjusted odds ratio=2.4, 95% confidence interval=1.2–4.8). Intervention providers viewed dementia patients as more difficult to manage in primary care than usual‐care providers (P=.03). There were no other differences in knowledge, attitudes, or care quality perceptions across intervention and usual‐care providers.CONCLUSION: A comprehensive dementia care management model resulted in few differences in provider knowledge or attitudes favorable to dementia care, suggesting that this care model's effects on quality were primarily mediated through other components of the care management program.
Osteoblast‐like cells are sensitive to submicron‐scale surface structure
Authors: Zhao Ge , Zinger Olivier , Schwartz Zvi , Wieland Marco , Landolt Dieter , Boyan Barbara D. 
Published: March 2006

AbstractObjectives: Studies showing that osteoblasts exhibit a more differentiated phenotype on rough titanium (Ti) surfaces and osteoclast‐resorbed bone surfaces used materials characterized by average peak to valley distance (Ra). Other surface features impacting the cells include distance between peaks, curvature of the valleys, and relative distribution of flat and smooth regions. We used novel Ti surfaces prepared by electrochemical micromachining as models to examine specific contributions of individual design features to osteoblast response. Results show that micron‐scale topography modulates cell number, cell morphology and prostaglandin E2 (PGE2). In the presence of the appropriate microtopography, submicron‐scale rugosity modulates differentiation and transforming growth factor‐β1 (TGF‐β1) levels. In this study, we examined the role of different types of submicron‐scale structures.Material and methods: Thirty micrometer diameter craters on Ti disks were produced by photolithography resulting in an electropolished smooth surface, and arranged so that inside crater area vs. outside flat area was 6 (30/6). Submicron‐scale structures were superposed by acid etching and porous anodization. Ra's were 700, 400, 60 nm on acid‐etched, porous anodized and smooth 30/6 surfaces, respectively.Results: MG63 osteoblast‐like cells were sensitive to submicron‐scale architecture. Cell morphology on anodized surfaces was similar to morphology on smooth surfaces, whereas on etched surfaces, cells had a more elongated differentiated shape. Cell number was greatest on smooth surfaces>anodized>etched. Osteocalcin and PGE2 were affected in a reverse manner. Active TGF‐β1 was greatest on etched 30/6 surfaces>anodized>smooth; latent TGF‐β1 was elevated on all rough surfaces.Conclusions: These results support our previous observations that submicron‐scale structures modulate osteoblastic phenotype and show that the physical properties of the submicron‐scale structures are important variables in determining osteoblast response to substrate topography.