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  • 1
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: In the present study the subacute effects of β-N-oxalylamino-l-alanine (BOAA) and β-N-methyIamino-l-alanine (BMAA) on CNS monoamine neurons in rats were investigated following intracisternal injections or local intracerebral administration into substantia nigra. In vitro effects of BOAA and BMAA on high-affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) were also examined. Intracisternal administration of BMAA decreased NA levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels. Following intranigral injections of BOAA, NA levels tended to decrease in several regions, whereas the DA levels and the levels of DA metabolites were unaffected in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in the intranigral injection sites and the presence of TH-immunoreactive pyknotic neurons near the borders of the injection sites were observed following both BOAA and BMAA treatments. Furthermore, substance P-immunoreactive terminals in substantia nigra pars reticulata were also found to have disappeared within the lesioned area following either BOAA or BMAA injections. Incubations with both BOAA and BMAA (10--5M) reduced high-affinity [3H]NA uptake in cortical synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high-affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can affect central monoamine neurons, although the potency and specificity of these substances on monoamine neurons when administered acutely into cerebral tissue or liquor cerebri seem to be low. However, the in vitro studies indicate selective effects of both compounds on NA neurons in synaptosomal preparations.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 3 (1991), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Brain-derived neurotrophic factor (BDNF) is a member of a family of related neurotrophic proteins which includes nerve growth factor (NGF) and hippocampus-derived neurotrophic factor/neurotrophin-3 (NT-3). To obtain information regarding possible roles for BDNF during postnatal brain development, we have examined the temporal and spatial expression of this trophic factor using in situ hybridization. In specific neocortical regions BDNF mRNA-expressing cells were seen at 2 weeks of age and thereafter. One particular neuronal cell type strikingly labelled was the inverted pyramidal cell population in the deep layers of parietotemporal cortex. In pyriform and cingulate cortices, BDNF mRNA was detected at postnatal day 1 and 1 week of age, respectively, with increasing levels during ontogeny. Several forebrain regions, including the thalamic anterior paraventricular nucleus, hypothalamic ventromedial nucleus as well as the preoptic area, contained moderate levels of BDNF mRNA throughout development. BDNF mRNA was detected transiently in several brainstem structures, notably in the substantia nigra and interpeduncular nucleus. Expression of this trophic factor in hippocampus was relatively low in the early neonatal brain, but attained high levels in the CA3 and CA4 regions as well as in the dentate gyrus by 2 weeks of age. At this early age, which is still during the period of neurogenesis in the dentate gyrus, labelling was restricted to the outer layer, which contained cells with a more mature appearance. However, by 3 weeks of age labelling was distributed throughout the granule cell layer. Our results show both transient and persistent expression of BDNF mRNA in various regions of the developing rat brain and suggest that there is a caudal to rostral gradient of BDNF expression during postnatal brain development, which may be correlated to neuronal maturation.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Nurr1 (Nr4a2) is a transcription factor expressed in dopamine cells from early development and throughout life. Null mutants for Nurr1 lack the ventral midbrain dopamine neurons and die soon after birth. Animals with a heterozygous deletion are viable and display no apparent abnormality. We have investigated the impact of heterozygous deletion of Nurr1 on ethanol consumption in adult mice as a model for drug-induced reward and on wheel running as a model for natural reward. Interestingly, Nurr1 heterozygous mice never developed high ethanol consumption nor did they develop as much running behaviour as did the wild-type animals. Thus, Nurr1 appears to have a key role for the reinforcing properties of ethanol and running that underlies the development of excessive reward-seeking behaviours characteristic for addiction. Quantitative trait loci mapping using C57Bl/6 and DBA/2 mice describe a locus for ethanol preference on chromosome 2, wherein Nurr1 is located. We found two dinucleotide repeats in the Nurr1 promoter that were longer in mice with low preference for ethanol (DBA/2 and 129/Sv) than in mice with high preference for ethanol (C57Bl/6J and C57Bl/6NIH). These sequential data are compatible with Nurr1 as a candidate gene responsible for the quantitative trait loci for ethanol preference on mouse chromosome 2. Together, our data thus imply involvement of Nurr1 in the transition to a state of high ethanol consumption as well as in the development of a high amount of wheel running in mice.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: We report here the identification of a gene, termed GFRα-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFRα-1 and GFRα-2 (also known as GDNFR-α and GDNFR-β), and describe distribution of GDNFα-3 in the nervous system and other parts of the mouse body during development and in the adult. GFRα-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFRα-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFRα-1 and GFRα-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFRα-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFRα-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFRα-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 18 (2003), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague–Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hotplate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Glial cell line-derived neurotrophic factor (GDNF) mRNA is highly expressed by dental pulp cells (DPCs) prior to the initiation of dental pulp innervation. We show that radioactively labelled exogenous GDNF is retrogradely transported from neonatal teeth and vibrissae to the trigeminal neurons, indicating that GDNF acts as a classical neurotrophic factor in the trigeminal system. We also show that DPCs from both rats and humans produce nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and GDNF mRNAs in vitro, promote the survival and phenotypic characteristics of embryonic dopaminergic (DA) neurons and protect DA neurons against the neurotoxin 6-hydroxy-dopamine (6-OHDA) in vitro. By using inhibitory antibodies to NGF, BDNF and GDNF, we show that the promotion of DA neuron survival relates to the production and release of neurotrophic proteins by DPCs in vitro. We suggest that in vivo production of neurotrophic factors by DPCs play roles in tooth innervation. However, continued production of neurotrophic factors by the DPCs might have wider implications. We propose that the dental pulp is a viable source of easily attainable cells with possible potential for development of autologous cell transplantation therapies. We also show that a population of neural crest-derived dental pulp cells acquire clear neuronal morphology and protein expression profile in vitro, indicating the presence of a cell population in the dental pulp with neuronal differentiation capacity that might provide additional benefits when grafted into the CNS.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Physical activities such as long-distance running can be habit forming and associated with a sense of well-being to a degree that justifies comparison with drug-induced addictive behaviours. To understand molecular similarities and dissimilarities controlling these behaviours in humans we compared the effects of running in running wheels to the effects of chronic cocaine or morphine administration on mRNA levels in brain reward pathways in the inbred Fischer and Lewis rat strains. These strains are both inbred from the Sprague–Dawley strain; Lewis rats display a higher preference towards addictive drugs and running than do Fischer rats. After chronic cocaine or running a similar increase of dynorphin mRNA in medial caudate putamen was found in the Lewis rat, suggesting common neuronal adaptations in this brain region to both cocaine and running. Fischer and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after running, possibly reflecting the much higher degree of running by the Lewis strain as compared to the Fischer strain. Moreover, the running-induced upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist naloxone. We suggest that running increases dynorphin mRNA by a mechanism that involves endogenous opioids. The voluntary wheel-running model in rats might be used to study natural reward and compulsive behaviours and possibly also to screen candidate drugs for treatment of compulsive disorders.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Retinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand-activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, α, β and γ. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP- and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I- and CRABP Iimmunoreactivity (IR). RXRβ is found in most areas while RARα and -β and RXRα and -γ show much more restricted patterns of expression. RARα is found in cortex and hippocampus and RARβ and RXRγ are both highly expressed in the dopamine-innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RARγ could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons. The CRBP I- and CRABP I-IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid-binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    [s.l.] : Nature Publishing Group
    Nature medicine 3 (1997), S. 1329-1335 
    ISSN: 1546-170X
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Medizin
    Notizen: [Auszug] Genes dictate development of the major cytoarchitectonic plan comprising the central nervous system. During formation, this plan may become disturbed for a variety of reasons, but once development is completed, the principle wiring diagram remains fixed. At the level of a single neuron and ...
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    [s.l.] : Nature America Inc.
    Nature biotechnology 18 (2000), S. 925-927 
    ISSN: 1546-1696
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: [Auszug] In perpetual search of better therapies for human afflictions, humankind is scouring the surrounding biosphere for plant- and animal-derived remedies. As it turns out, transplantation of living cells offers particularly rich possibilities. Cells can be grafted to replace lost cells, provide ...
    Materialart: Digitale Medien
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