bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akt is altered in an animal model of Huntington's disease and in patients
Authors: Colin Emilie , Régulier Etienne , Perrin Valérie , Dürr Alexandra , Brice Alexis , Aebischer Patrick , Déglon Nicole , Humbert Sandrine , Saudou Frédéric 
Published: January 2009

AbstractThe insulin‐like growth factor I (IGF‐1)/Akt pathway plays a crucial role in Huntington's disease by phosphorylating the causative protein, polyQ‐huntingtin, and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831–837; Rangone et al. (2004)Eur. J. Neurosci., 19, 273–279]. Therefore, dysregulation of this pathway may be essential for disease progression. In the present report, we thus aimed to analyse the status of Akt in brain or in peripheral tissues in Huntington's disease. Using a genetic model of Huntington's disease in rat that reproduces neuronal dysfunction and death, we show a progressive alteration of Akt during neuronal dysfunction and prior neurodegeneration. By analysing a limited number of lymphoblasts and lymphocytes, we detected modifications of Akt in Huntington's disease patients confirming a dysregulation of Akt in the disease process. Finally, we demonstrate that during late stages of the disease, Akt is cleaved into an inactive form by caspase‐3. These observations demonstrate a progressive but marked alteration of this pro‐survival pathway in Huntington's disease, and further implicate it as a key transduction pathway regulating the toxicity of huntingtin.
Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP
Authors: Lam Chen Sok , Korzh Vladimir , Strahle Uwe 
Published: January 2009

AbstractThe neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induces selective loss of dopaminergic neurons in the mammalian midbrain, eliciting symptoms characteristic of Parkinson's disease. By exploiting the advantages of zebrafish embryos, we report here that dopaminergic neurons in this species are specifically perturbed when exposed to MPTP. In contrast to mammals, the zebrafish does not possess a midbrain dopaminergic system. Instead, the main population of neurons expressing the dopamine transporter is located in the posterior tuberculum of the diencephalon. Exposure of embryos to MPTP led to a pronounced reduction in the number of dopaminergic cells in the diencephalon. This effect can be reversed by deprenyl, a specific inhibitor of monoamine oxidase B that catalyses the conversion of MPTP to its active metabolite, MPP+. Similarly, direct treatment of embryos with MPP+ abolished the diencephalic dopaminergic neurons. These larvae also demonstrated behavioural defects in swimming responses. Thus, dopaminergic neurons in the posterior tuberculum of the zebrafish may be homologous to the midbrain dopaminergic system of mammals. In addition, the mechanism behind the loss of dopaminergic neurons following pharmacological perturbation may be conserved among vertebrates and suggest that the zebrafish can be used as a convenient and economical system to study the pathogenesis of Parkinson's disease and for testing potential therapeutic strategies.
Antagonist‐induced supersensitivity of mGlu1 receptor signalling in cerebellar granule cells
Authors: Lavreysen Hilde , Willemoens Tineke , Leysen Joseé E. , Lesage Anne S. J. 
Published: January 2009

AbstractWe investigated the effect of 24 h sustained treatment with the mGlu1 receptor antagonist CPCCOEt on mGlu1 receptor signalling in primary cultures of rat cerebellar granule cells. In the absence of ionotropic glutamate (iGlu) blockers, the maximal inositol phosphate (IP) response (Emax) but not the potency of glutamate was significantly increased when cells were pre‐exposed for 24 h with CPCCOEt. When the contribution of iGlu receptors to the glutamate‐induced IP response was eliminated with the use of DNQX, the Emaxwas again increased but also the concentration eliciting 50% of the maximal glutamate stimulus was significantly decreased. In the absence of iGlu receptor inhibitors, the Emaxof quisqualate, which likely mediates IP accumulation only via the mGlu1 receptor, was significantly increased in CPCCOEt‐pretreated cells. Also, less quisqualate was needed to reach the same IP effect. The potency of R193845, a selective mGlu1 receptor antagonist, was significantly decreased in antagonist‐pretreated cells. These findings demonstrate that 24 h sustained antagonist treatment can render mGlu1 receptors in neurons supersensitive to agonists, with a concomitant decrease in the effectiveness of antagonists.
Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset monkey
Authors: Pryce Christopher R. , Feldon Joram , Fuchs Eberhard , Knuesel Irene , Oertle Thomas , Sengstag Christian , Spengler Marianne , Weber Elizabeth , Weston Anna , Jongen‐Rélo Ana 
Published: January 2009

AbstractThe mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are nuclear transcription factors that mediate many of the basal and stress functions and effects of the corticosteroid hormones, including those related to brain development. Despite this, relatively little is known about the postnatal ontogeny of MR and GR gene and protein expression in the central nervous system, and this is particularly true of the primates, including humans. Here we describe the postnatal ontogeny of central MR and GR gene and protein expression in the common marmoset monkey. By developing marmoset‐specific riboprobes and usingin situhybridization, it was demonstrated that MR mRNA expression in the dentate gyrus and Ammon's horn was significantly greater in marmoset infants (aged 4–6 weeks) than in neonates (1–2 days), juveniles (4–5 months) and adults (3–6 years), with expression in the latter three ontogenetic stages being broadly similar. In the same subjects and ontogenetic stages, GR mRNA expression was developmentally consistent in the marmoset dentate gyrus and Ammon's horn, as well as in the paraventricular nucleus of the hypothalamus. Qualitative immunohistochemical comparison of infants and adults demonstrated that MR protein expression in the hippocampus was, as for mRNA, also greater in infants than adults, and that hippocampal GR protein was, as for mRNA, also similar in infants and adults. The increase in MR mRNA expression between the stages of neonate and infant co‐occurred with a reduction in basal plasma ACTH and cortisol titres. The ontogenetic profiles of MR and GR gene expression in the marmoset monkey are therefore fundamentally different from those described for the rat and the mouse. This evidence for the postnatal ontogeny of central corticosteroid nuclear receptor expression in a primate is important for understanding both the developmental stage‐specific significance of stress exposure and its potential long‐term effects on health and disease.
Voluntary exercise rescues deficits in spatial memory and long‐term potentiation in prenatal ethanol‐exposed male rats
Authors: Christie Brian R. , Swann Sarah E. , Fox Christopher J. , Froc David , Lieblich Stephanie E. , Redila Van , Webber Alina 
Published: January 2009

AbstractPrenatal ethanol exposure can lead to long‐lasting impairments in the ability to process spatial information in rats, as well as produce long‐lasting deficits in the ability of animals to exhibit long‐term potentiation, a biological model of learning and memory processing. Conversely, we have recently shown that both spatial memory and long‐term potentiation can be enhanced in animals that are given access to a running wheel in their home cage. In the present study, Sprague–Dawley rat dams were given one of three diets throughout gestation: (i) a liquid diet containing ethanol (35.5% ethanol‐derived calories); (ii) a liquid diet, isocaloric to the ethanol diet, but with maltose‐dextrin substituting for the ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At weaning (28 days) animals were housed individually in either a standard rat cage, or a cage that contained a running wheel. Adult offspring were tested on a two trial version of the Morris water maze beginning at postnatal day 60, for five consecutive days. Following this, the capacity of the perforant path to dentate gyrus pathway to sustain long‐term potentiation was examined in these animals using theta‐patterned conditioning stimuli. Our results demonstrate that prenatal ethanol exposure can produce pronounced deficits in both spatial memory and long‐term potentiation, but that allowing animal's access to voluntary exercise can attenuate these deficits to the point that those exposed to ethanol prenatally can no longer be differentiated from control animals. These findings indicate that voluntary exercise may have therapeutic benefits for individuals that have undergone prenatal ethanol exposure.
Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat
Authors: Iczkiewicz Joanna , Rose Sarah , Jenner Peter 
Published: January 2009

AbstractNigral cell death in Parkinson's disease is characterized by glial cell activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated phosphoprotein that is induced by inflammatory mediators and which we have previously shown to be present in the substantia nigra. However, the role of OPN in the nigral inflammation is not known. We now report on the effects of lipopolysaccharide (LPS)‐induced glial cell activation in the substantia nigra of rats on OPN expression. LPS administration induced dopaminergic cell death as shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a corresponding time‐dependent increase in both OPN mRNA, which was maximal at 48 h, and protein levels, which peaked at 72 h before returning to control levels by 120 h. This increase was accompanied by marked reactive gliosis as shown by increased OX‐42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity. OX‐42‐positive cells increased in a time‐dependent manner, peaking at 72 h before returning to control levels at 120 h. Similarly, ED1‐positive cells were present in their greatest numbers at 24 h but then gradually declined. These changes mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In contrast, GFAP‐positive cells only started to increase in number at 120 h. Colocalization studies showed that OPN was present in both ED1‐ and OX‐42‐positive cells but not in GFAP‐positive cells. These data confirm that intranigral injection of LPS induces a rapid and marked gliosis that accompanies the loss of tyrosine hydroxylase‐positive neurones and suggest that, after glial cell activation, enhanced expression of OPN occurs linked to increased numbers of microglia and/or macrophages. This suggests that OPN may be functionally important in the control of inflammatory changes.
Selective effects of partial striatal 6‐OHDA lesions on information processing in the rat
Authors: Courtière Alain , Hardouin Jeannine , Locatelli Virginie , Turle‐Lorenzo Nathalie , Amalric Marianne , Vidal Franck , Hasbroucq Thierry 
Published: January 2009

AbstractThe present study was aimed at characterizing the cognitive deficits caused by the degeneration of nigrostriatal dopamine (DA) pathways by using the additive factor logic [Sternberg, S. (1969) Acta Psychol., 30, 276–315], a powerful reaction time (RT) method developed in humans and recently introduced in the rat [Courtière, A., Hardouin, J., Hasbroucq, T., Possamaï, C.‐A. & Vidal, F. (2000) Behav. Process., 50, 113–121]. Long‐Evans rats were trained to respond to left or right (lateral) visual cues in a choice RT task. Two task factors, signal intensity and force requirement, were manipulated. Partial bilateral 6‐OHDA lesions of DA nerve terminals in the striatum were then performed and their effects tested for up to 7 weeks following surgery. Reaction time was lengthened from the 2nd to the 4th week postlesion. This alteration was independent of force requirement, thereby suggesting that the related motor processes were not influenced by the DA depletion. During the 2nd week postlesion, the RT increase was accompanied by a disappearance of the effect of signal intensity, showing that the lesion altered stimulus‐related processes. From the 3rd week the signal intensity effect was re‐established although RT was still increased, indicating that the stimulus‐related processes had recovered while other central processes were still impaired. From the 5th week after surgery, the lesioned animals had completely recovered from the RT deficits induced by the lesion. These results point at the involvement of striatal DA in sensory and central information processes.
Development of pontine noradrenergic A5 neurons requires brain‐derived neurotrophic factor
Authors: Guo Hong , Hellard David T. , Huang Lennox , Katz David M. 
Published: January 2009

AbstractPontine noradrenergic A5 neurons play a pivotal role in maturation and regulation of the brainstem respiratory rhythm‐generating network. Analysis of newborn brain‐derived neurotrophic factor (BDNF)‐null mice revealed a marked loss of tyrosine hydroxylase‐positive A5 neurons compared to wildtype controls that was rescued by null mutation of the proapoptotic gene Bax. In cultures of the A5 region from E12.5 rat embryos, BDNF significantly increased the number and branching of tyrosine hydroxylase‐positive neurons. Immunoneutralization of endogenous glial cell line‐derived neurotrophic factor partially inhibited the BDNF‐dependent increase in the number of tyrosine hydroxylase‐positive cells without affecting neurite number. The A5 nucleus is the first brainstem cell group identified at which BDNF is required in vivo for development of neurons critical for cardiorespiratory control.
Multiple defects in the formation of rat cortical axonal pathways following prenatal X‐ray irradiation
Authors: Li Hong‐Peng , Honma Shizuka , Miki Takanori , Takeuchi Yoshiki , Takeuchi Kosei , Kawano Hitoshi 
Published: January 2009

AbstractPrenatal X‐ray irradiation is known to result in severe defects of neuronal migration and laminar formation in the cerebral cortex. We examined the formation of cortical afferent and efferent pathways in rats that had been exposed to X‐ray irradiation (1.0 Gy) at embryonic day 14 (E14), by birthdating with bromodeoxyuridine (BrdU) and axonal labeling with 1‐1′‐dioctodecyl‐3,3,3′,3′‐ tetramethyl‐indocarbocyanine perchlorate (DiI), in addition to immunohistochemical staining for various axonal markers including neurofilament, and cell adhesion molecules L1 and TAG‐1. The results obtained were as follows. (i) The neuroepithelium formed germinal rosettes and concavities in the cortical anlage from 2 days after irradiation. Neurons generated in the neuroepithelium accumulated to form subcortical heterotopia and obstructed pathway formation in the intermediate zone, resulting in an aberrant trajectory of TAG‐1‐immunoreactive cortical efferent axons. (ii) In rats exposed to X‐ray irradiation at E14, cystic cavities were formed in the cortex–striatum boundary region between E15 and E17, probably because of delayed cell death of neurons generated at E14. These cavities transiently interrupted both cortical afferent (L1‐positive) and efferent (TAG‐1‐positive) axons. (iii) X‐ray irradiation at E14 partially destroyed subplate neurons (transient targets of thalamic afferent axons) and disturbed the arrangement of the subplate layer. This resulted in a misrouting of neurofilament‐ and L1‐immunoreactive thalamocortical axons that obliquely traversed the cortical plate to run up to the superficial layer. The present study demonstrates for the first time that X‐ray irradiation during initial cortical development causes multiple defects in the formation of cortical afferent and efferent pathways.
Right‐hemisphere motor facilitation by self‐descriptive personality‐trait words
Authors: Molnar‐Szakacs Istvan , Uddin Lucina Q. , Iacoboni Marco 
Published: January 2009

AbstractThe emergent picture from the literature on the processing of self‐related information suggests that in addition to the neural mechanisms involved in recognizing one's own face, there may also be neural representations of the self that are modality independent and favour the right hemisphere. We used focal, single‐pulse transcranial magnetic stimulation in human subjects to assess cortical excitability during covert reading of self‐descriptive personality‐trait words. We hypothesized that the right hemisphere would show a greater overall facilitation to personality‐trait words than the left hemisphere. Overall, personality‐trait words led to significantly greater motor facilitation in the right hemisphere than in the left hemisphere. In addition, words rated as ‘never’ self‐characteristic yielded significant right hemisphere facilitation, and words rated as ‘always’ self‐characteristic showed a similar trend. The results are discussed in terms of the notion that the right hemisphere plays a dominant role in both self‐relevant processing and the processing of affective stimuli.
A pentylenetetrazole‐induced generalized seizure in early life enhances the efficacy of muscarinic receptor coupling to G‐protein in hippocampus and neocortex of adult rat
Authors: Potier Soizic , Sénécal Jacques , Chabot Jean‐Guy , Psarropoulou Caterina , Descarries Laurent 
Published: January 2009

AbstractWe have previously shown that exposure to the anti‐cholinesterase eserine provokes interictal‐like discharges in the CA3 area of hippocampal slices from adult rats in which a generalized seizure has been induced by pentylenetetrazole (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine (ACh) was not associated with any change in hippocampal acetylcholine or γ‐aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh innervation, but was blocked by the muscarinic receptor antagonist atropine. We therefore turned to quantitative radioligand binding autoradiography,in situhybridization and the [35S]GTPγS method to assess the properties of hippocampal and neocortical muscarinic receptors in adult rats having experienced a PTZ seizure at P20. The densities of M1 and M2 receptor binding sites, respectively labeled with [3H]pirenzepine and [3H]AFDX‐384, as well as the amount of m1, m2 and m3 receptor mRNAs, did not differ from control in the hippocampus and neocortex of these rats. In contrast, in PTZ rats, both brain regions displayed a marked increase in [35S]GTPγS incorporation stimulated by ACh, bethanechol and particularly oxotremorine. This finding indicates that a generalized seizure in immature rat can entail a long‐term and presumably permanent increase in the efficacy of G‐protein coupling to muscarinic receptors in the hippocampus and neocortex of the adult. By analogy, such a mechanism could account for the susceptibility to epilepsy of human adults having suffered from prolonged convulsions in early life.
Target‐controlled inhalation induction with sevoflurane in children: a prospective pilot study
Authors: FRITSCH NICOLAS , NOUETTE‐GAULAIN KARINE , BORDES MARYLINE , SEMJEN FRANCOIS , MEYMAT YVES , CROS ANNE‐MARIE 
Published: January 2009

SummaryBackground:  Target‐controlled inhalation induction (TCII) with sevoflurane is becoming possible with new anesthesia platforms. Although TCII has already been performed in adults, it remains to be evaluated in children.Methods:  In a prospective study, we compared TCII using the Felix AInOC™ anesthetic station (Taema, Anthony, France) to our standard protocol inhalation induction in children scheduled for elective surgery under general anesthesia. After preoxygenation, sevoflurane induction was performed in both groups without priming of the circuit. Sufentanil was administered after venous line placement.Results:  In the TCII group, no overdosage or underdosage was observed except in two children where TCII failed owing to high agitation, and the number of adjustments was lower compared with our standard protocol inhalation induction (1(1–2.5[0–5]) vs 6(5–6[4–10]) respectively). Moreover, the delay to obtain target end‐tidal sevoflurane concentration was shorter in the TCII group (2(1.6–2.7[1.3–4]) min vs 3.4(2.5–3.8[2.3–6.5]) min respectively). No significant difference in the delay of loss of consciousness or in the conditions for intubation or laryngeal mask placement was observed between the groups.Conclusion:  The Felix AInOC™ allows TCII to be performed satisfactorily in children. Manual inhalation induction induced a higher number of adjustments and overdosages.
Noncolonic cancer stem cells in bone marrow of colorectal cancer patients
Authors: Altomare D. F. , Guanti G. , Hoch J. , Vician M. , Krivokapic Z. , Bergamaschi R. ,   for the Colorectal Micrometastases Study Group (see )
Published: January 2009

AbstractObjective  To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates.Method  Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 × 106 BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single‐strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI‐positive patients were isolated with immunobeads coated with magnetically labelled anti‐human epithelial antigen antibody and DNA‐screened for mutations.Results  Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow‐up. Twenty‐five (2–170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty‐two patients developed LM at 36‐month follow‐up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer‐specific death rates, or all death rates.Conclusions  Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.
Colonic diverticulitis: a prospective analysis of diagnostic accuracy and clinical decision‐making
Authors: Toorenvliet B. R. , Bakker R. F. R. , Breslau P. J. , Merkus J. W. S. , Hamming J. F. 
Published: January 2009

AbstractObjective  To evaluate the diagnostic accuracy of clinical evaluation and cross‐sectional imaging modalities such as ultrasound and computed tomography for patients with suspected colonic diverticulitis and to determine the value of these examinations in clinical decision‐making.Method  A prospective analysis was conducted of 802 consecutive patients that presented with abdominal pain at the emergency department. Initial clinical diagnoses and management proposals were compared to the final diagnoses and therapeutic strategies for all patients.Results  Fifty‐seven patients were identified with colonic diverticulitis as the final diagnosis. The positive and negative predictive values for the clinical diagnosis of colonic diverticulitis were 0.65 and 0.98 respectively. Additional cross‐sectional imaging had a positive and negative predictive value of respectively 0.95 and 0.99 or higher. These additional examinations led to a correct change of the initial clinical diagnosis in 37% of the patients, and a change in management in only 7%.Conclusion  The accuracy of the clinical diagnosis for colonic diverticulitis is low. Ultrasound and computed tomography have superior diagnostic accuracy but these examinations rarely change the initial management proposal.