bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with a CDR2 BV6S2/6S5 peptide in adjuvant induces peptide‐specific T‐cell responses in patients with multiple sclerosis
Authors: Morgan Elizabeth E. , Nardo Christopher J. , Diveley Jocelyn P. , Kunin Joel , Bartholomew Richard M. , Moss Ronald B. , Carlo Dennis J. 
Published: October 2004

AbstractEarlier studies from several groups including ours have documented that patients with multiple sclerosis (MS) have over‐expression of activated T‐cells from specific TCR Vβ families, including BV6S2/S5 (Kotzin et al. [1991] Proc. Natl. Acad. Sci. USA 88:9161–9165; Gold et al. [1997] J. Neuroimmunol. 76:29–38). It has also been established in the rat EAE model that peptide vaccines to the over‐expressed Vβ 8.2 TCR can prevent MBP induced disease (Vandenbark et al. [1989] Nature 341:541–544). In the current clinical study, 10 patients were vaccinated with 300 μg of BV6S2/6S5 peptide emulsified in incomplete Freund's adjuvant (IFA) and monitored for safety and immunogenicity in a 48‐week multicenter, open‐label trial. The peptide vaccine was well tolerated and no serious adverse events were observed. Vaccinations induced cell‐mediated immunity to the immunizing peptide in eight of 10 patients as demonstrated by lymphocyte proliferation assay (LPA) and delayed‐type hypersensitivity (DTH) skin test responses. In summary, these results demonstrate that immunization with TCR BV6S2/6S5 peptide vaccine in MS patients is safe and immunogenic, and supports a larger double‐blind placebo controlled trial to determine the clinical efficacy of this approach. J. Neurosci. Res. 64:298–301, 2001. © 2001 Wiley‐Liss, Inc.
Neuronal and glial β‐secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology
Authors: Roßner Steffen , Apelt Jenny , Schliebs Reinhard , Perez‐Polo J. Regino , Bigl Volker 
Published: October 2004

AbstractWe measured tissue distribution and expression pattern of the beta‐site amyloid precursor protein (APP)‐cleaving enzyme (BACE) in the brains of transgenic Tg2576 mice that show amyloid pathology. BACE protein was expressed at high levels in brain; at lower levels in heart and liver; and at very low levels in pancreas, kidney, and thymus and was almost absent in spleen and lung when assayed by Western blot analysis. We observed strictly neuronal expression of BACE protein in the brains of nontransgenic control mice, with the most robust immunocytochemical labeling present in the cerebral cortex, hippocampal formation, thalamus, and cholinergic basal forebrain nuclei. BACE protein levels did not differ significantly between control and transgenic mice or as a result of aging. However, in the aged, 17‐month‐old Tg2576 mice there was robust amyloid plaque formation, and BACE protein was also present in reactive astrocytes present near amyloid plaques, as shown by double immunofluorescent labeling and confocal laser scanning microscopy. The lack of astrocytic BACE immunoreactivity in young transgenic Tg2576 mice suggests that it is not the APP overexpression but rather the amyloid plaque formation that stimulates astrocytic BACE expression in Tg2576 mice. Our data also suggest that the neuronal overexpression of APP does not induce the overexpression of its metabolizing enzyme in neurons. Alternatively, the age‐dependent accumulation of amyloid plaques in the Tg2576 mice does not require increased neuronal expression of BACE. Our data support the hypothesis that neurons are the primary source of β‐amyloid peptides in brain and that astrocytic β‐amyloid generation may contribute to amyloid plaque formation at later stages or under conditions when astrocytes are activated. J. Neurosci. Res. 64:437–446, 2001. © 2001 Wiley‐Liss, Inc.
mDll1 and mDll3 expression in the developing mouse brain: Role in the establishment of the early cortex
Authors: Campos Lia Scotti , Duarte António José , Branco Tiago , Henrique Domingos 
Published: October 2004

AbstractThe Delta/Notch signalling system is involved in several developmental processes. During fly neurogenesis, Delta expression defines the fate of neuronal precursors and inhibits neighboring Notch‐expressing cells from acquiring a neural fate, a process known as lateral inhibition. In vertebrates, recent evidence demonstrates that Notch activation can positively determine cell fate and affect neuronal process extension. Nevertheless, Delta‐like expression patterns during brain development are relatively unknown. Using a transgenic mouse, which expresses LacZ under the mDll1 promoter, we show by immunofluorescence that in the developing telencephalon mDll1 is expressed in undifferentiated cells in close contact with radial glial cells. Based on in situ hybridization data on mDll1 and mDll3 mRNA expression and on the immunohistochemical detection of β‐galactosidase in the Dll1‐lacZ transgenic mouse, we suggest that mDll1 and mDll3 are involved in the establishment of the early cortical plate and that mDll1‐expressing cells are in close contact with radial glial cells, thereby modulating the latter population, which is known to express Notch1. Furthermore, we suggest that the decrease in mDll1 mRNA found toward the end of gestation could be related, first, to the slowing of neurogenesis and, second, to the differentiation of the radial glial cell population into astrocytes. J. Neurosci. Res. 64:590–598, 2001. © 2001 Wiley‐Liss, Inc.
GABAA receptor gene expression in rat cortex: Differential effects of two chronic diazepam treatment regimes
Authors: Arnot Michelle I. , Davies Martin , Martin Ian L. , Bateson Alan N. 
Published: October 2004

AbstractDiazepam is widely prescribed as an anxiolytic but its therapeutic application is limited because with daily use tolerance develops to certain aspects of its pharmacological profile. We compared the effects of two dosing paradigms on GABAA receptor gene expression and benzodiazepine binding characteristics. Equivalent daily doses of 15 mg/kg/day diazepam were delivered either via constant infusion or daily subcutaneous injection for 14 days. The two distinct treatment regimes produced significantly different changes in GABAA receptor α4‐, β2‐, β3‐ and γ1‐subunit mRNA steady‐state levels. Similar changes in the GABA enhancement of flunitrazepam binding and the BZ3/BZ2 subtype ratio determined ex vivo were produced, however, significant differences were found in [3H]‐Ro 15‐4513 binding between cortical tissue from diazepam injected animals compared with diazepam infused animals. Our data suggest that it is the diurnal fluctuations in receptor occupancy that are responsible for the different effects produced by these two dosing regimes. J. Neurosci. Res. 64:617–625, 2001. © 2001 Wiley‐Liss, Inc.
CREM and ICER are differentially implicated in trans‐synaptic induction of tyrosine hydroxylase gene expression in adrenal medulla and sympathetic ganglia of rat
Authors: Trocmé C. , Ravassard P. , Sassone‐Corsi P. , Mallet J. , Faucon Biguet N. 
Published: October 2004

AbstractReserpine treatment leads to a trans‐synaptic increase of the tyrosine hydroxylase (TH) gene transcription rate, mRNA and protein levels in catecholaminergic tissues including the adrenal medulla (AM) and the superior cervical ganglia (SCG). The TPA‐responsive element plays an important role in the trans‐synaptically‐induced transcription of the TH gene in the AM, whereas it does not appear to be involved in the SCG (Trocmé et al. [1997] J. Neurosci. Res. 48:489–498). In this study, we show that another regulatory sequence of the TH proximal promoter, the cAMP‐responsive element (CRE), binds different factors in the AM and in the SCG. To elucidate the dynamics of promoter regulation a complete time course analysis was conducted. Reserpine treatment enhances, between 1 hr and 8 hr after the injection, the expression and the binding of the repressor ICER in the AM, whereas in the SCG it enhances the binding of CREM factors. These results suggest that the mechanisms mediating trans‐synaptic induction of the TH gene are different in the AM and SCG. The interplay between positive and negative transcription factors and their kinetics of action are responsive of the long‐term regulation of the TH gene. J. Neurosci. Res. 65:91–99, 2001. © 2001 Wiley‐Liss, Inc.
Neural recognition molecule NB‐2 of the contactin/F3 subgroup in rat: Specificity in neurite outgrowth‐promoting activity and restricted expression in the brain regions
Authors: Ogawa Junko , Lee Suni , Itoh Kouichi , Nagata Saburo , Machida Takeo , Takeda Yasuo , Watanabe Kazutada 
Published: October 2004

AbstractNB‐2, a neural cell recognition molecule of the contactin/F3 subgroup, promoted neurite outgrowth of the cerebral cortical neurons but not the hippocampal neurons. NB‐2 in rat became apparent after birth at protein level, reaching a maximum at postnatal day 14 in the cerebrum and postnatal day 3 in the cerebellum. NB‐2 in the cerebellum declined abruptly thereafter. In situ hybridization demonstrated that NB‐2 mRNA was highly expressed in regions implicated in the central auditory pathway, including the cochlear nuclei, superior olive, inferior colliculi, medial geniculate nuclei, and auditory cortex. In addition, a high level of NB‐2 expression was observed in the accessory olfactory bulb, thalamic nuclei, facial nucleus, and inferior olive. By immunohistochemistry, intense immunoreactivity against NB‐2 was also detected in the auditory pathway. Thus, NB‐2 is expressed in highly restricted brain regions, including the auditory system, suggesting that it plays specific roles in the development and/or maturation of the regions. J. Neurosci. Res. 65:100–110, 2001. © 2001 Wiley‐Liss, Inc.
Target‐dependent modulation of neurotransmitter release in cultured Helix neurons involves adhesion molecules
Authors: Ghirardi Mirella , Naretto Giuseppe , Fiumara Ferdinando , Vitiello Francesco , Montarolo Pier Giorgio 
Published: October 2004

AbstractThe secretory capabilities of the serotonergic neuron C1 of cerebral ganglion of Helix pomatia were markedly reduced when it was cultured in contact with the wrong target neuron, C3. When the neuron B2, one of its physiological targets, was micromanipulated within the network made of intermingled neurites originating from the axonal stumps of both C1 and C3 neurons, C1 increased the amount of the evoked transmitter release, which, after 30 min, reached the level observed when cocultured with the appropriate target. The removal of the appropriate target brought C1 back to the low release condition. By imaging C1 neurites with a fluorescent dye, morphological changes involving a local increase in the number of varicosities could be observed as early as 30 min after contact with the appropriate target. Monoclonal antibody 4E8 against apCAM, a family of Aplysia adhesion molecules, recognizes apCAM‐like molecules of the Helix central nervous system on immunocytochemistry and Western blot analysis. The contact with the appropriate target previously incubated in a 4E8 solution, which did not interfere with its capacity to respond to serotonin, failed to increase the transmitter release of C1 cocultured in the presence of the wrong target, C3. These results suggest that the apCAM‐like antigens bound to the target membrane participate in the molecular processes responsible for the assembly of the “release machinery” present in the functional presynaptic structure. J. Neurosci. Res. 65:111–120, 2001. © 2001 Wiley‐Liss, Inc.
Developmental expression of a voltage‐dependent potassium channel (Kv3.1) in auditory neurons without cochlear input
Authors: Feng Jane , Morest D. Kent 
Published: October 2004

AbstractKv3.1, a voltage‐dependent potassium channel, has two forms, ‐a and ‐b, which differ in expression during development and at the onset of function in the auditory system. To determine whether cochlear nerve input could affect the expression of these two forms, cultures of the developing cochlear nucleus were explanted in the absence of the cochlear nerve at the beginning of cell migration (Hamburger‐Hamilton stage 28–30), while neuroblasts continued to migrate onto the culture substrate. After 8, 15, and 22 days in vitro (three survival groups), cultures were immunostained with antibodies recognizing either both forms of Kv3.1 or only the ‐b form. Only young and newly migrated nerve cells were sampled. In the three survival groups, all nerve cells expressed Kv3.1, among which only 50% or less expressed the ‐b form. Some of the more differentiated multipolar cells expressed the ‐b form, but most were labeled with the antibody that recognizes both forms. Thus, in the absence of peripheral input, both forms of Kv3.1 appear at stages very early in development, although not all cells necessarily coexpress both forms. These results agree with other observations in the chick embryo in situ. They are consistent with previous work implicating Kv3.1 in cell migration during early development. J. Neurosci. Res. 65:121–128, 2001. © 2001 Wiley‐Liss, Inc.
Agonists calcitonin, corticotropin‐releasing hormone, and vasoactive intestinal peptide, but not prostaglandins or β‐adrenergic agonists, elevate cyclic adenosine monophosphate levels in oligodendroglial cells
Authors: Wiemelt Anthony P. , Lehtinen Maria , McMorris F. Arthur 
Published: October 2004

AbstractAlthough 3′,5′‐cyclic AMP (cAMP) is known to regulate oligodendrocyte development in vitro, little is known about the identity of agonists that induce cAMP synthesis in oligodendroglia. To identify such agonists, we used a novel immunohistochemical method of visualizing cAMP within single cells to screen compounds that are known to activate cAMP synthesis in other cellular systems. Calcitonin, corticotropin‐releasing hormone, and vasoactive intestinal peptide elevated cAMP in oligodendroglial cells but not in other cell types present in the cultures (i.e., astrocytes and microglia). In contrast, prostaglandins and the β‐adrenergic agonist isoproterenol, which have previously been reported to induce modest increases in oligodendroglial cell cAMP from biochemical assay of cell homogenates, did not induce a detectable cAMP response in individually identified oligodendroglial cells but instead induced a robust cAMP response in nonoligodendroglial cells. J. Neurosci. Res. 65:165–172, 2001. © 2001 Wiley‐Liss, Inc.
Oligodendroglia in the avian retina: Immunocytochemical demonstration in the adult bird
Authors: Seo Je Hoon , Haam Young Gil , Park Sang Wook , Kim Dong Woon , Jeon Gye Sun , Lee Cheol , Hwang Douk Ho , Kim Yong‐Sik , Cho Sa Sun 
Published: October 2004

AbstractImmunohistochemical techniques were used in conjunction with an avian‐specific probe for oligodendrocyte (OLG) marker, the antibody for transferrin binding protein (TfBP), to study the characteristics and distribution of OLGs in the retina of chickens and quails. For comparison, other antibodies such as myelin basic protein, Rip, and those for labeling Müller cells and microglia were used. A large population of OLGs was found to be distributed throughout the retina, with the distinct pattern of a central‐to‐peripheral gradient. It was possible to detect a spectrum of OLG morphology that bore a resemblance to the subtype of the mammalian central nervous system. In addition to these mature OLGs, limited numbers of TfBP‐positive (TfBP+) cells with the morphology of immature OLGs were found in the immediate vicinity of the optic head. The majority of OLGs appeared in the ganglion cell layer throughout the retina, whereas OLGs in the nerve fiber layer were seen mainly in the central zone of the retina, near the optic nerve head. Double‐labeling experiments showed that OLGs were associated with myelin only in the central region, where the majority of retinal OLGs occurred, but not toward the periphery of the retina. The present study is the first comprehensive analysis of the morphological features and spatial distribution of OLGs in the adult avian retina and provides in vivo evidence for the existence of a substantial population of both mature and immature OLGs in the retina of adult birds. The putative functions of TfBP+ OLGs including myelination and the tropic role of the ganglion cells are discussed in conjunction with the physical properties of TfBP and structural characteristics of the avascular retina of birds. J. Neurosci. Res. 65:173–183, 2001. © 2001 Wiley‐Liss, Inc.
Classic and soma‐restricted proteolipids are targeted to different subcellular compartments in oligodendrocytes
Authors: Bongarzone Ernesto R. , Jacobs Erin , Schonmann Vilma , Campagnoni Anthony T. 
Published: October 2004

AbstractThe myelin proteolipid (PLP) gene is very active in oligodendrocytes (OLs) and generates at least four proteins: the classic PLP and DM20 proteolipids, which are associated with compact myelin and the srPLP and srDM20, which are associated with the cell soma. These proteins are extremely hydrophobic and appear to follow the biosynthetic route used by secretory proteins. In this study, we have analyzed the subcellular distribution of the newly described sr‐proteolipids and compared it to that of the classic proteolipids. Immunocytochemical analysis indicates that the sr‐proteolipids and classic proteolipids are found in association with the endoplasmic reticulum (ER) and Golgi apparatus of mature OLs in vitro. Whereas the classic proteolipids become associated with the myelin‐like sheets elaborated by OLs, the sr‐proteolipids are not targeted to the myelin leaflets. The sr‐proteolipids were associated with endosomes and with recycling vesicles as determined by double immunocytochemistry with markers such as syntaxin 6 and clathrin. In vivo, immunohistochemical analysis showed a distribution of the sr‐proteolipids that was similar to that obtained in vitro, with a total absence of incorporation of sr‐proteolipids into compact myelin. This differential subcellular localization is further evidence for a biological role for these products of the PLP/DM20 gene, which is different from that of the classic proteolipids. J. Neurosci. Res. 65:477–484, 2001. © 2001 Wiley‐Liss, Inc.
Disulfide‐mediated dimerization of L1 Ig domains
Authors: Haspel Jeffrey , Schürmann Gregor , Jacob Jeffrey , Erickson Harold P. , Grumet Martin 
Published: October 2004

AbstractThe neural cell adhesion molecule L1 contains immunoglobulin‐like (Ig) domains in its extracellular region that mediate homophilic binding, neurite outgrowth and other activities relevant to CNS development. To correlate conformations of these domains to biological function, several L1‐Fc fusion proteins whose bioactivities were previously characterized were analyzed by rotary shadowing electron microscopy. We found that bioactive L1‐Fcs containing Ig domains 1–4 or 1–6 exhibited extended, branched structures. In contrast, inactive L1‐Fcs containing only the first two or three Ig domains assumed compact shapes that suggested interactions between the L1 arms of these proteins. Analysis of an untagged L1 fragment composed of Ig domains 1‐3 demonstrated a mixture of monomeric and dimeric forms. Surprisingly, these dimers were stabilized by intermolecular disulfide bonds. Finally, cell surface L1‐GFP fusion proteins containing only the first two or three Ig domains in the extracellular region also engaged in disulfide‐mediated dimerization. These results suggest a novel mechanism by which mutations in L1 could interfere with its biological functioning. J. Neurosci. Res. 66:347–355, 2001. © 2001 Wiley‐Liss, Inc.
Inhibition of nuclear factor‐κB activation induces apoptosis in cerebellar granule cells
Authors: Piccioli Patrizia , Porcile Carola , Stanzione Sabrina , Bisaglia Michela , Bajetto Adriana , Bonavia Rudy , Florio Tullio , Schettini Gennaro 
Published: October 2004

AbstractThe nuclear factor (NF)‐κB family of transcription factors plays important roles in the regulation of many activities of neuronal cells, such as synaptic transmission, inflammation, neuroprotection, and neurotoxicity. In resting cells, NF‐κB activity is present both in the cytoplasm, as an inducible‐inactive complex, and in the nucleus, as a constitutive form. Regulation of its inducible activity relies on processing of IκB(s), which occurs through the proteasome. Here we show that in cerebellar granule cells (CGC) the induction of apoptosis, by potassium withdrawal (5 mM KCl), decreases the amount of nuclear NF‐κB. To understand whether NF‐κB was required for CGC survival, these cells, maintained under depolarizing conditions (25 mM KCl and serum), were treated with proteasome inhibitors. The results show that these treatments reduce the nuclear amount of NF‐κB and increase p65 cytoplasmic levels, a process partially regulated via IκBα degradation. These events are also associated with an impairment in CGC survival, with changes in nuclear morphology, induction of DNA laddering, and oligonucleosome formation, consistent with apoptosis. According to the K+ deprivation model, PSI‐induced apoptosis is reversed by inhibitors of transcription and translation as well as by specific caspase inhibitors. Together our results show an important role for NF‐κB in maintaining CGC survival. Indeed, under conditions of mild depolarization (K25) necessary for CGC survival, NF‐κB is distributed between cytosol and nucleus, whereas, under apoptotic conditions (K5), it is depleted from the nucleus, such as after proteasome inhibitor treatment. Therefore, NF‐κB nuclear deprivation is involved in the induction of CGC apoptosis. J Neurosci. Res. 66:1064–1073, 2001. © 2001 Wiley‐Liss, Inc.
Kainic acid and seizure‐induced Fos in subtypes of cerebrocortical neurons
Authors: Hiscock Jennifer J. , Mackenzie Lorraine , Medvedev Andrei , Willoughby John O. 
Published: October 2004

AbstractKainic acid injected in vivo into adult rats evokes the expression of the immediate early gene c‐fos in the dentate gyrus and associated structures before a seizure occurs and in these and additional regions after a single motor seizure. The aim of this study was to identify cortical cell classes expressing Fos that correlate with these phenomena. Fos expression occurred before a seizure in the middle layers of entorhinal cortex in excitatory neurons and predominantly in calbindin D28‐K‐containing inhibitory neurons. Given the early Fos‐labeling of these cells, we suggest they are associated with the hippocampal EEG events also seen at this stage of the effects of kainic acid. After a motor seizure Fos induction occurred in primary motor, sensory, piriform and entorhinal cortices, mainly in excitatory neurons, but also in a proportion of calcium binding protein‐containing neurons proportionate to the degree of activation of the region as determined by Fos. Nearly 100% of neurons were Fos+ in entorhinal cortex, whereas 80% of excitatory and 50% of calcium binding protein‐containing neurons were Fos+ in piriform cortex with lower proportions in neocortex. Of the calcium binding protein‐containing neocortical neurons, calbindin D28‐K cells exhibited the highest proportion of double labeling with Fos. This pattern of neocortical activation by kainic acid, a glutamate agonist, is only slightly different to that seen after seizures caused by blockade of gamma aminobutyric acid receptors suggesting that seizures caused by different mechanisms utilize similar neo‐cortical circuitry. J Neurosci. Res. 66:1094–1100, 2001. © 2001 Wiley‐Liss, Inc.