bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transsynaptic virus tracing from host brain to subretinal transplants
Authors: Seiler Magdalene J. , Sagdullaev Botir T. , Woch Gustaw , Thomas Biju B. , Aramant Robert B. 
Published: January 2005

AbstractThe aim of this study was to establish synapses between a transplant and a degenerated retina. To tackle this difficult task, a little‐known but well‐established CNS method was chosen: trans‐synaptic pseudorabies virus (PRV) tracing. Sheets of E19 rat retina with or without retinal pigment epithelium (RPE) were transplanted to the subretinal space in 33 Royal College of Surgeons (RCS) and transgenic s334ter‐5 rats with retinal degeneration. Several months later, PRV‐BaBlu (expressing E. coliβ‐galactosidase) or PRV‐Bartha was injected into an area of the exposed superior colliculus (SC), topographically corresponding to the transplant placement in the retina. Twenty normal rats served as controls. After survival times of 1–5 days, retinas were examined for virus by X‐gal histochemistry, immunohistochemistry and electron microscopy. In normal controls, virus was first seen in retinal ganglion cells and Müller glia after 1–1.5 days, and had spread to all retinal layers after 2–3 days. Virus‐labeled cells were found in 16 of 19 transplants where the virus injection had retrogradely labeled the topographically correct transplant area of the host retina. Electron microscopically, enveloped and nonenveloped virus could clearly be detected in infected cells. Enveloped virus was found only in neurons. Infected glial cells contained only nonenveloped virus. Neurons in retinal transplants are labeled after PRV injection into the host brain, indicating synaptic connectivity between transplants and degenerated host retinas. This study provides evidence that PRV spreads in the retina as in other parts of the CNS and is useful to outline transplant–host circuitry.
Antioxidant metabolite profiles in tomato fruit constitutively expressing the grapevine stilbene synthase gene
Authors: Giovinazzo Giovanna , D’Amico Leone , Paradiso Annalisa , Bollini Roberto , Sparvoli Francesca , DeGara Laura 
Published: January 2005

SummaryTomato (Lycopersicon esculentum Mill.) tissues were transformed with a grape (Vitis vinifera L.) stilbene synthase cDNA, transcriptionally regulated by the cauliflower mosaic virus (CaMV) 35S promoter. Transgenic plants accumulated new compounds, not present in either wild‐type or vector‐transformed plants. These were identified, by high‐pressure liquid chromatography, as trans‐resveratrol and trans‐resveratrol‐glucopyranoside. The amounts of trans‐resveratrol and its piceid form were evaluated in the transgenic fruit. It was found that the content of the metabolite varied during fruit maturation to up to 53 µg/g fresh weight of total trans‐resveratrol at the red stage of ripening. This metabolite accumulation was possibly dependent on a combination of sufficiently high levels of stilbene synthase and the availability of substrates. With the aim of verifing the metabolic impairment, the amounts of chlorogenic acid and naringenin in both transgenic and wild‐type ripening fruit were compared and no dramatic variation in the synthesis profile of the two metabolites was noted. To our knowledge, no data are available on the assessment of the effects of the expression of the StSy gene on other antioxidant compounds present in tomato fruit. To establish whether the presence of a novel antioxidant molecule affected the redox regulation in transgenic tomato fruit cells, the effect of resveratrol accumulation on the naturally present antioxidant pool was analysed. We showed that, in transgenic fruit which accumulate trans‐resveratrol, there is an increase in the levels of ascorbate and glutathione, the soluble antioxidants of primary metabolism, as well as in the total antioxidant activity. Conversely, the content of tocopherol and lycopene, which are membrane‐located antioxidants, is not affected. Consistent with the increased antioxidant properties, the lipid peroxidation was lower in transformed than in wild‐type fruit.
Experiences from Teaching Statistics Using Directed Projects in Greek Elementary School
Authors: Ghinis D. , Chadjipantelis Th. , Bersimis S. 
Published: January 2005

SummaryIn this article, we present the main findings of an experiment which involves teaching statistics in the 5th and 6th grade classes of Greek elementary schools. This experiment focused on the evaluation of the potentials of teaching statistical concepts and methods using directed projects.
The influence of perinatal complications and environmental adversity on boys’ antisocial behavior
Authors: Beck Joy E. , Shaw Daniel S. 
Published: January 2005

Background:  The purpose of the present study was to test components of biosocial model, specifically the interactive effects of perinatal complications, rejecting parenting, and family adversity on the development of early‐onset antisocial behavior (ASB). Boys’ internalizing problems were also tested to investigate the specificity of the model.Methods:  Birth records in addition to longitudinal data were collected on 310 low‐income boys followed from birth until 10 years of age.Results:  Findings demonstrated support for a biosocial framework in predicting ASB but not internalizing problems. Family adversity, and to some extent rejecting parenting, consistently predicted youth outcome. Perinatal complications emerged as a predictor of ASB but only in the context of other family risk factors. According to maternal report, boys experiencing high levels of perinatal complications, rejecting parenting, and family adversity showed significantly higher levels of ASB than boys with lower levels of these risk factors. This finding was partially corroborated by youth self‐report, such that boys experiencing high levels of perinatal complications and family adversity reported more antisocial activity than boys experiencing no risk or risk in only one domain.Conclusions:  This study supports the specific prediction of ASB in middle childhood from a biosocial model. Findings also highlight the salience of a negative psychosocial environment on childhood maladjustment. Intervention efforts including parenting skills and coping strategies for mothers of children from multiple risk environments are advocated.
Time‐course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging
Authors: Manczak Maria , Jung Youngsin , Park Byung S. , Partovi Dara , Reddy P. Hemachandra 
Published: January 2005

AbstractThe study of aging is critical for a better understanding of many age‐related diseases. The free radical theory of aging, one of the prominent aging hypotheses, holds that during aging, increasing reactive oxygen species in mitochondria causes mutations in the mitochondrial DNA and damages mitochondrial components, resulting in senescence. Understanding a mitochondrial gene expression profile and its relationship to mitochondrial function becomes an important step in understanding aging. The objective of the present study was to determine mRNA expression of mitochondrial‐encoded genes in brain slices from C57BL6 mice at four ages (2, 12, 18, and 24 months) and to determine how these altered mitochondrial genes influence age‐related changes, including oxidative damage and cytochrome c in apoptosis. Using northern blot analysis, in situ hybridization, and immunofluorescence analyses, we analyzed changes in the expression of mitochondrial RNA encoding the mitochondrial genes, oxidative damage marker, 8‐hydroxyguanosine (8‐OHG), and cytochrome c in brain slices from the cortex of C57BL6 mice at each of the four ages. Our northern blot analysis revealed an increased expression of mitochondrial‐encoded genes in complexes I, III, IV, and V of the respiratory chain in 12‐ and 18‐month‐old C57BL6 mice compared to 2‐month‐old mice, suggesting a compensatory mechanism that allows the production of proteins involved in the electron transport chain. In contrast to the up‐regulation of mitochondrial genes in 12‐ and 18‐month‐old C57BL6 mice, mRNA expression in 24‐month‐old C57BL6 mice was decreased, suggesting that compensation maintained by the up‐regulated genes cannot be sustained and that the down‐regulation of expression results in the later stage of aging. Our in situ hybridization analyses of mitochondrial genes from the hippocampus and the cortex revealed that mitochondrial genes were over‐expressed, suggesting that these brain areas are critical for mitochondrial functions. Our immunofluorescence analysis of 8‐OHG and cytochrome c revealed increased 8‐OHG and cytochrome c in 12‐month‐old C57BL6 mice, suggesting that age‐related mitochondrial oxidative damage and apoptosis are associated with mitochondrial dysfunction. Our double‐labeling analysis of in situ hybridization of ATPase 6 and our immunofluorescence analysis of 8‐OHG suggest that specific neuronal populations undergo oxidative damage. Further, double‐labeling analysis of in situ hybridization of ATPase 6 and immunofluorescence analysis of cytochrome c suggest cytochrome c release is related to mitochondrial dysfunction in the aging C57BL6 mouse brain. This study also suggests that these mitochondrial gene expression changes may relate to the role of mitochondrial dysfunction, oxidative damage, and cytochrome c in aging and in age‐related diseases such as Alzheimer's disease and Parkinson's disease.
Protective effects of insulin‐like growth factor‐I on the somatostatinergic system in the temporal cortex of β‐amyloid‐treated rats
Authors: Aguado‐Llera D. , Arilla‐Ferreiro E. , Campos‐Barros A. , Puebla‐Jiménez L. , Barrios V. 
Published: January 2005

AbstractInsulin‐like growth factor‐I (IGF‐I) has protective effects against β‐amyloid (Aβ)‐induced neuronal cell death. Because alterations of the somatostatinergic system have been described in Alzheimer's disease, we investigated the effects of the Aβ peptide and the possible protective role of IGF‐I on the somatostatinergic system of the rat temporal cortex and on cell death and phosphorylated (p)‐Akt levels in this area. Aβ25–35 was administered intracerebroventricularly to male rats via an osmotic minipump over 14 days (300 pmol/day). Another group received a subcutaneous IGF‐I infusion (50 μg/kg/day), concomitant with Aβ25–35 administration, whereas a third group received IGF‐I alone. Aβ25–35 significantly decreased the somatostatin (SRIF)‐like immunoreactive content and the SRIF receptor density, as a result of a decrease in the levels of the SRIF receptor subtype 2. The inhibitory effect of SRIF on adenylyl cyclase activity was significantly lower after Aβ25–35 infusion, whereas the levels of the inhibitory G protein subunit Giα1, Giα2 or Giα3 were unaltered. Cell death was increased and p‐Akt levels decreased in Aβ25–35‐treated animals. IGF‐I administration increased immunoreactive IGF‐I levels in the temporal cortex and restored all parameters affected by Aβ25–35 to baseline values. These findings suggest that IGF‐I prevents the deleterious effect of Aβ25–35 on the somatostatinergic system.
Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain
Authors: Groffen Alexander J. A. , Jacobsen Linda , Schut Désireé , Verhage Matthijs 
Published: January 2005

AbstractTomosyn was previously identified as a syntaxin‐binding protein that inhibits soluble NSF (n‐ethylmaleimide‐sensitive fusion protein) attachment protein receptor (SNARE)‐mediated secretion. We set out to investigate the distribution of tomosyn mRNA in the mammalian brain and found evidence for the presence of two paralogous genes designated tomosyn‐1 and ‐2. In a collection of tomosyn‐2 cDNA clones, we observed four splice variants (named xb‐, b‐, m‐ and s‐tomosyn‐2) derived from the skipping of exons 19 and 21. This feature is conserved with tomosyn‐1 that encodes three splice variants. To compare the expression pattern of tomosyn‐1 and ‐2, we performed in situ hybridization experiments with gene‐specific probes. Both genes were expressed in the nervous system, clearly following distinct spatial and developmental expression patterns. Real‐time quantitative PCR experiments indicated that tomosyn‐1 expression was up‐regulated less than threefold between developmental stages E10 and P12, whereas tomosyn‐2 expression increased 31‐fold. Not only the transcription level, but also the splice composition of tomosyn‐2 mRNA shifted during development. We conclude that two distinct genes drive expression of seven tomosyn isoforms. Their expression patterns support a role in regulating neuronal secretion. All isoforms share conserved WD40 and SNARE domains separated by a hypervariable module, the function of which remains to be clarified.
Differential effects of melanin concentrating hormone on the central dopaminergic neurons induced by the cocaine‐ and amphetamine‐regulated transcript peptide
Authors: Yang Shu‐Chuan , Shieh Kun‐Ruey 
Published: January 2005

AbstractStimulatory effects of cocaine‐ and amphetamine‐regulated transcript (CART) peptide on central mesolimbic, nigrostriatal and mesocortical dopaminergic (DA) neurons were examined in female Sprague–Dawley rats. We also determined the different blocking effects of melanin concentrating hormone (MCH) on the stimulation by CART peptide in central DA systems. Intracerebroventricular administration of 1 µg CART peptide (55–102) produced increases in 3,4‐dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens (NA) at 15 and 45 min, and in the striatum (ST) at 15 min, but not in the medial prefrontal cortex (MPFC). We found that the agonist of α‐melanocyte stimulating hormone (α‐MSH), MT II, at 10 µg had a stimulatory effect on the NA and ST DOPAC levels similar to the CART peptide. In contrast, 1 µg MCH and the antagonist of α‐MSH, HS014, significantly decreased NA and ST DOPAC levels. However, only MCH prevented the stimulatory effect of CART peptide on DOPAC levels in the NA, but not in the ST. These results indicate that the stimulation of CART peptide on central DA neurons is region‐specific, and that this effect can be blocked by MCH but not by the antagonist of α‐MSH.
Neuronal calcium sensor‐1 facilitates neuronal exocytosis through phosphatidylinositol 4‐kinase
Authors: Zheng Qian , Bobich Joseph A. , Vidugiriene Jolanta , McFadden Susanne C. , Thomas Fairwell , Roder John , Jeromin Andreas 
Published: January 2005

AbstractThis work tested the theory that neuronal calcium sensor‐1 (NCS‐1) has effects on neurotransmitter release beyond its actions on membrane channels. We used nerve‐ending preparations where membrane channels are bypassed through membrane permeabilization made by mechanical disruption or streptolysin‐O. Nerve ending NCS‐1 and phosphatidylinositol 4‐kinase (PI4K) are largely or entirely particulate, so their concentrations in nerve endings remain constant after breaching the membrane. Exogenous, myristoylated NCS‐1 stimulated nerve ending phosphatidylinositol 4‐phosphate [PI(4)P] synthesis, but non‐myristoylated‐NCS‐1 did not. The N‐terminal peptide of NCS‐1 interfered with PI(4)P synthesis, and with spontaneous and Ca2+‐evoked release of both [3H]‐norepinephrine (NA) and [14C]‐glutamate (glu) in a concentration‐dependent manner. An antibody raised against the N‐terminal of NCS‐1 inhibited perforated nerve ending PI(4)P synthesis, but the C‐terminal antibody had no effects. Antibodies against the N‐ and C‐termini of NCS‐1 caused significant increases in mini/spontaneous/stimulation‐independent release of [3H]‐NA from perforated nerve endings, but had no effect on [14C]‐glu release. These results support the idea that NCS‐1 facilitates nerve ending neurotransmitter release and phosphoinositide production via PI4K and localizes these effects to the N‐terminal of NCS‐1. Combined with previous work on the regulation of channels by NCS‐1, the data are consistent with the hypothesis that a NCS‐1–PI4K (NP, neuropotentiator) complex may serve as an essential linker between lipid and protein metabolism to regulate membrane traffic and co‐ordinate it with ion fluxes and plasticity in the nerve ending.
Ampakine™ CX546 bolsters energetic response of astrocytes: a novel target for cognitive‐enhancing drugs acting as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor modulators
Authors: Pellerin Luc , Magistretti Pierre J. 
Published: January 2005

AbstractGlutamate was previously shown to enhance aerobic glycolysis i.e. increase glucose utilization and lactate production with no change in oxygen levels, in mouse cortical astrocytes by a mechanism involving glutamate uptake. It is reported here that a similar response is produced in both hippocampal and cerebellar astrocytes. Application of the cognitive‐enhancing drug CX546 promoted further enhancement of glucose utilization by astrocytes from each brain area following glutamate exposure. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors represent the purported molecular target of cognitive‐enhancing drugs such as CX546, and the presence of AMPA receptor subunits GluR1–4 was evidenced in astrocytes from all three regions by immunocytochemistry. AMPA itself did not stimulate aerobic glycolysis, but in the presence of CX546, a strong enhancement of glucose utilization and lactate production was obtained in cortical, hippocampal and cerebellar astrocytes. The effect of CX546 was concentration‐dependent, with an EC50 of 93.2 µm in cortical astrocytes. AMPA‐induced glucose utilization in the presence of CX546 was prevented by the AMPA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and the negative modulator GYKI 52466. In addition, the metabolic effect of CX546 in the presence of AMPA was mimicked by the AMPA receptor modulator cyclothiazide. Our data suggest that astrocyte energetics represents a novel target for cognitive‐enhancing drugs acting as AMPA receptor modulators.
C‐terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
Authors: Boeckers Tobias M. , Liedtke Thomas , Spilker Christina , Dresbach Thomas , Bockmann Jürgen , Kreutz Michael R. , Gundelfinger Eckart D. 
Published: January 2005

AbstractSynapses are specialized contact sites mediating communication between neurons. Synaptogenesis requires the specific assembly of protein clusters at both sides of the synaptic contact by mechanisms that are barely understood. We studied the synaptic targeting of multi‐domain proteins of the ProSAP/Shank family thought to serve as master scaffolding molecules of the postsynaptic density. In contrast to Shank1, expression of green‐fluorescent protein (GFP)‐tagged ProSAP1/Shank2 and ProSAP2/Shank3 deletion constructs in hippocampal neurons revealed that their postsynaptic localization relies on the integrity of the C‐termini. The shortest construct that was perfectly targeted to synaptic sites included the last 417 amino acids of ProSAP1/Shank2 and included the C‐terminal sterile alpha motif (SAM) domain. Removal of 54 residues from the N‐terminus of this construct resulted in a diffuse distribution in the cytoplasm. Altogether, our data delineate a hitherto unknown targeting signal in both ProSAP1/Shank2 and ProSAP2/Shank3 and provide evidence for an implication of these proteins and their close homologue, Shank1, in distinct molecular pathways.
Tournefolic acid B methyl ester attenuates glutamate‐induced toxicity by blockade of ROS accumulation and abrogating the activation of caspases and JNK in rat cortical neurons
Authors: Chi Chih‐Wen , Wang Chuen‐Neu , Lin Yun‐Lian , Chen Chieh‐Fu , Shiao Young‐Ji 
Published: January 2005

AbstractThe effects of nine polyphenolic compounds on glutamate‐mediated toxicity were investigated. The underlying mechanisms by which a polyphenolic compound confers its effect were also elucidated. Treatment of cortical neurons with 50 µm glutamate for 24 h decreased cell viability by 45.8 ± 7.9%, and 50 µm of tournefolic acid B methyl ester attenuated glutamate‐induced cell death by 46.8 ± 17.8%. Glutamate increased the activity of caspase 35.2‐fold, and to a similar extent for caspase 2, 6, 8 and 9. Tournefolic acid B methyl ester abrogated glutamate‐induced activation of caspase 2, 3, 6 and 9 by about 70%, and to a lesser extent for caspase 8. Treatment with glutamate for 1 h elevated reactive oxygen species (ROS) by 208.3 ± 21.3%. Tournefolic acid B methyl ester eliminated the glutamate‐induced accumulation of ROS. Glutamate increased the phosphorylation of p54‐c‐jun N‐terminal kinase (JNK) concomitantly with activation of the endogenous antioxidant defense system. Tournefolic acid B methyl ester at 50 µm diminished the activity of p54‐JNK in control and glutamate‐treated cells, coinciding with the abolishment of the glutamate‐triggered antioxidant defense system. Therefore, tournefolic acid B methyl ester blocked the activation of the caspase cascade, eliminated ROS accumulation and abrogated the activation of JNK, thereby conferring a neuroprotective effect on glutamate‐mediated neurotoxicity.
Musical hallucinations induced by bromocriptine
Authors: KOBAYASHI Toshiyuki , MIYATA Yoshifumi , OKAMOTO Sohei , KATO Satoshi 
Published: January 2005

AbstractA case of bromocriptine‐induced musical hallucinations in a 67‐year‐old patient with probable Lewy body dementia is reported. The patient was given bromocriptine for the treatment of parkinsonism. At a bromocriptine dosage of  7.5 mg,  the  patient  complained,  ‘I  hear  karaoke  songs  in  the  inner  part of my head.’ The musical hallucinations gradually decreased after administration of the drug was discontinued. Bromocriptine is known to cause hallucinations, but not musical hallucinations. The dopaminergic effect of bromocriptine and the patient's cognitive impairment might have acted together to generate the musical hallucinations.
Early diagnosis of Alzheimer's type dementia with special reference to the clinicopathology of mild cognitive impairment
Authors: IKEDA Kenji , MIZUNO Yutaka , AKIYAMA Haruhiko , IRITANI Shuji , MATSUSHITA Masaaki 
Published: January 2005

AbstractA considerable number of patients with Alzheimer‐type pathology begin with various types of psychiatric symptoms. In discussing mild cognitive impairment (MCI) and Alzheimer‐type dementia (ATD), psychiatric symptoms other than memory impairment must be considered. There is no obvious neuropathological boundary that distinguishes dementia from non‐dementia. In fact, although Alzheimer‐type pathology of MCI corresponds mainly to Braak's stage I or II, it has a wide range extending from Braak's stage I to V or VI. Difference in compensatory ability and environmental factors among individuals seem to affect the mental state more extensively than previously thought. MCI manifests most frequently in Braak's stage I and II (transentorhinal stage) and its Alzheimer‐type pathology is almost confined to the hippocampal region. Although the degree and distribution of senile plaques vary in each patient, the cerebral isocortex is virtually free from degeneration. There is discrepancy between the corresponding neuropathology and hypo‐metabolism in the posterior cingulated cortex (PCC), which is regarded as an important finding for the early diagnosis of ATD. In PCC, hypo‐metabolism seems to precede that morphological change especially in its premorbid or early period of ATD. The state of MCI could also occur in other diseases causing dementia, among which tangle‐only dementia is particularly notable. The characteristic of tangle‐only dementia is the gradually progressive, persistent pathological memory impairment with relative preservation of personality and cognitive function. These characteristics meet the criteria for MCI. Thus, tangle‐only dementia should be taken into account in patients who exhibit MCI but do not progress to the development of dementia over a prolonged period.