Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: KNOCKOUT MICE ; CLINICAL-IMPLICATIONS ; NUCLEUS-ACCUMBENS ; PARKINSONS-DISEASE ; OPIATE-SEEKING BEHAVIOR ; CA2+ CHANNEL BLOCKERS ; STRAUB TAIL REACTION ; LOCOMOTOR-ACTIVITY ; COMBINATIONS SPEEDBALL ; INDUCED HYPERACTIVITY
    Abstract: Considerable topographic overlap exists between brain opioidergic and dopaminergic neurons. Pharmacological blockade of the dopamine D-1 receptor (Drd1 a) reverses several behavioural phenomena elicited by opioids. The present study examines the effects of morphine in adult mutant (MUT) mice expressing the attenuated diphtheria toxin-176 gene in Drd1a-expressing cells, a mutant line shown previously to undergo post-natal striatal atrophy and loss of Drd1a-expression. MUT and wild-type mice were assessed behaviourally following acute administration of 10 mg/kg morphine. Treatment with morphine reduced locomotion and rearing similarly in both genotypes but reduced total grooming only in MUT mice. Morphine-induced Straub tail and stillness were heightened in MUT mice. Chewing and sifting were decreased in MUT mice and these effects were not modified by morphine. Loss of striatal Drd1-positive cells and up-regulated D-2-expression, as reflected in down-regulated D-1-like and up-regulated D-2-like binding, respectively, is not uniform along the cranio-caudal extent in this model but appears to be greater in the caudal striatum. Preferential caudal loss of mu-opioid-expression, a marker for the striosomal compartment, was seen. These data indicate that Drd1a-positive cell loss modifies the exploratory behavioural response elicited by morphine, unmasking novel morphine-induced MUT-specific behaviours and generating a hypersensitivity to morphine for others.
    Type of Publication: Journal article published
    PubMed ID: 23337398
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: TRANSGENIC MICE ; WORKING-MEMORY ; AMYOTROPHIC-LATERAL-SCLEROSIS ; KNOCKOUT MICE ; CEREBRAL-CORTEX ; HUNTINGTONS-DISEASE MUTATION ; RAT PREFRONTAL CORTEX ; RISK GENE NEUREGULIN-1 ; YAC128 MOUSE MODEL ; STRIATAL NEURONAL LOSS
    Abstract: D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIalpha(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIalpha(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia.
    Type of Publication: Journal article published
    PubMed ID: 25684539
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: brain ; RECEPTOR ; CELLS ; CELL ; SUPPORT ; MICE ; TIME ; MECHANISM ; mechanisms ; BINDING ; DISORDER ; MEMORY ; PHENOTYPES ; AGE ; PHENOTYPE ; STRATEGIES ; DISORDERS ; ADULT ; interaction ; adaptation ; therapeutic ; STRATEGY ; hypothesis ; Young Adult
    Abstract: In this study we characterize the behavioural and cellular phenotype of mutant (MUT) mice with progressive loss of D1 dopamine receptor (Drd1a)-expressing cells. Adult [14-19 weeks] MUT mice showed intact working memory in the spontaneous alternation test but evidenced anxiety-like behaviour in the elevated plus maze and the light-dark test. The ethogram of mature adult MUT [average age 22 weeks] was compared with that of young adult MUT mice [average age 12 weeks]. While MUT mice evidenced hyperactivity over initial exploration at both time points, the topography of hyperactivity shifted. Moreover, initial hyperactivity was sustained over habituation at 12 weeks, but not at 22 weeks. Thus, by 22 weeks MUT mice evidenced shifts in, and mitigation of, these early phenotypic effects. However, orofacial behaviours of chewing and sifting were reduced similarly at 12 and 22 weeks. These data support the hypothesis that aspects of the mutant phenotype change with time. Quantitative autoradiography at 20 weeks revealed loss of D1-like dopamine receptor binding in the entire basal ganglia, with upregulated D2-like binding. There appear to be topographically specific interactions between normal maturational processes and compensatory mechanisms evoked subsequent to targeted ablation of D1 dopamine receptor-expressing cells. Understanding the mechanistic bases of mitigation vs persistence of individual phenotypes in relation to neural adaptation consequent to cell loss may lead to novel therapeutic strategies for basal ganglia disorders.
    Type of Publication: Journal article published
    PubMed ID: 19733597
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: GENE ; AGE ; BEHAVIOR ; NEURONS ; HUNTINGTONS-DISEASE ; KNOCKOUT MICE ; SYMPTOMS ; ONSET ; sex ; Huntington's disease ; dopamine receptors ; orofacial ; PSYCHOPHARMACOLOGY
    Abstract: Orofacial movements were quantified in (a) DARPP-32/Cre D1Tox mutants, having progressive loss of D1 dopamine receptor expressing striatal medium spiny neurons and (b) CamKIIa/Cre D1Tox mutants, having progressive, generalized loss of forebrain D1 receptor expressing cells. Horizontal jaw movements and tongue protrusions were reduced in DARPP-32/Cre but not in CamKIIa/Cre mutants; head and vibrissae movements were increased in DARPP-32/Cre but decreased in CamKIIa/Cre mutants. In drug challenge studies, tongue protrusions were increased in CamKIIa/Cre mutants following vehicle, suggesting a stress-related phenotype. These findings indicate that mice with progressive loss of striatal-specific D1 receptor expressing cells have an orofacial phenotype that may be modulated by the loss of extrastriatal D1 receptor expressing cells. As progressive loss of D1 dopamine receptor-expressing cells is a hallmark feature of Huntington's disease (HD), these findings may inform the functional role of loss of this cell population in the overall pathobiology of HD.
    Type of Publication: Journal article published
    PubMed ID: 21308794
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: IN-VIVO ; CENTRAL-NERVOUS-SYSTEM ; HUNTINGTONS-DISEASE ; NEURAL STEM-CELLS ; adult neurogenesis ; OLFACTORY-BULB ; BRAIN-INJURY ; ASTROCYTE DEVELOPMENT ; AGED BRAIN ; OLIG2
    Abstract: BACKGROUND: Mice generated by a Cre/LoxP transgenic paradigm were used to model neurodegenerative basal ganglia disease of which Huntington disease (HD) is the prototypical example. In HD, death occurs in striatal projection neurons as well as cortical neurons. Cortical and striatal neurons that express the D1 dopamine receptor (Drd1a) degenerate in HD. The contribution that death of specific neuronal cell populations makes to the HD disease phenotype and the response of the brain to loss of defined cell subtypes is largely unknown. METHOD: Drd1a-expressing cells were targeted for cell death and three independent lines generated; a striatal-restricted line, a cortical-restricted line and a global line in which Drd1a cells were deleted from both the striatum and cortex. Two independent experimental approaches were used. In the first, the proliferative marker Ki-67 was used to identify proliferating cells in eighty-week-old mice belonging to a generic global line, a global in which Drd1a cells express green fluorescent protein (GFP-global) and in eighty-week-old mice of a cortical line. In the second experiment, the proliferative response of four-week-old mice belonging to GFP-global and striatal lines was assessed using the thymidine analogue BrdU. The phenotype of proliferating cells was ascertained by double staining for BrdU and Olig2 (an oligodendrocyte marker), Iba1 (a microglial cell marker), S100beta (an astroglial cell marker), or NeuN (a neuronal cell marker). RESULTS: In the first study, we found that Ki-67-expressing cells were restricted to the striatal side of the lateral ventricles. Control mice had a greater number of Ki-67+ cells than mutant mice. There was no overlap between Ki-67 and GFP staining in control or mutant mice, suggesting that cells did not undergo cell division once they acquired a Drd1a phenotype. In contrast, in the second study we found that BrdU+ cells were identified throughout the cortex, striatum and periventricular region of control and mutant mice. Mutant mice from the GFP-global line showed increased BrdU+ cells in the cortex, striatum and periventricular region relative to control. Striatal line mutant mice had an increased number of BrdU+ cells in the striatum and periventricular region, but not the cortex. The number of microglia, astrocytes, oligodendrocytes and neurons generated from dividing progenitors was increased relative to control mice in most brain regions in mutant mice from the GFP-global line. In contrast, striatal line mutant mice displayed an increase only in the number of dividing microglia in striatal and periventricular regions. CONCLUSIONS: Genetically programmed post-natal ablation of Drd1a-expressing neurons is associated with an extensive proliferative response involving multiple cell lineages. The nature of the tissue response has the potential not only to remove cellular debris but also to forge physiologically meaningful brain repair. Age related deficits in proliferation are seen in mutant lines. A blunted endogenous reparative response may underlie the cumulative deficits characteristic of age related neurodegeneration.
    Type of Publication: Journal article published
    PubMed ID: 24090101
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: brain ; RECEPTOR ; CELLS ; EXPRESSION ; IN-VITRO ; CELL ; MODEL ; VOLUME ; DEATH ; DISEASE ; MICE ; MESSENGER-RNA ; REDUCTION ; MRI ; MAGNETIC-RESONANCE ; TRANSGENIC MICE ; MAGNETIC-RESONANCE SPECTROSCOPY ; LINE ; CLINICAL-DIAGNOSIS ; INCREASE ; CRE ; NEURONS ; HUNTINGTONS-DISEASE ; IMPAIRMENT ; analysis ; function ; LOSSES ; animal ; neuron ; TARGETED EXPRESSION ; Huntington's disease ; striatum ; TOXIN GENE
    Abstract: Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate an animal model in which D1 dopamine receptor (Drd1a)+ cells are progressively ablated in the postnatal brain. Striatal Drd1a, substance P, and dynorphin expression is progressively lost, whereas D2 dopamine receptor (Drd2) and enkephalin expression is up-regulated. Magnetic resonance spectroscopic analysis demonstrated early elevation of the striatal choline/creatine ratio, a finding associated with extensive reactive striatal astrogliosis. Sequential MRI demonstrated a progressive reduction in striatal volume and secondary ventricular enlargement confirmed to be due to loss of striatal cells. Mutant mice had normal gait and rotarod performance but displayed hindlimb dystonia, locomotor hyperactivity, and handling-induced electrographically verified spontaneous seizures. Ethological assessment identified an increase in rearing and impairments in the oral behaviors of sifting and chewing. In line with the limbic seizure profile, cell loss, astrogliosis, microgliosis, and down-regulated dynorphin expression were seen in the hippocampal dentate gyrus. This study specifically implicates Drd1a+ cell loss with tail suspension hindlimb dystonia, hyperactivity, and abnormal oral function. The latter may relate to the speech and swallowing disturbances and the classic sign of tongue-protrusion motor impersistence observed in Huntington's disease. In addition, the findings of this study support the notion that Drd1a and Drd2 are segregated on striatal projection neurons
    Type of Publication: Journal article published
    PubMed ID: 17360497
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Heat and mass transfer 20 (1986), S. 255-261 
    ISSN: 1432-1181
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Description / Table of Contents: Zusammenfassung Es wird die exakte analytische Lösung für den allgemeinen Fall der kontinuierlichen Stoffübertragung zwischen einem Festkörper mit biporöser Struktur (Mikro- und Makroporosität) und einer im Gegenstrom fließenden Fluid-Phase vorgestellt. Der Transport in dem Feststoff erfolgt mittels molekularer Diffusion. Außerhalb der Feststoffpartikel wird der konvektive Filmwiderstand berücksichtigt. Eine allgemeine Formel wird angegeben, die für die unendliche Platte, für den unendlichen Zylinder und für die Kugel anwendbar ist. Die Lösung für das übliche monopore Modell ergibt sich als Sonderfall.
    Notes: Abstract This paper presents the exact analytical solution for the general case of continuous mass transfer between a solid with a biporous structure (micro and macroporosity) and a countercurrent flowing fluid phase. The transport inside the solid is by molecular diffusion and outside of it the convective film resistance is included. A general expression is given which is valid for the infinite plate, for the infinite cylinder and for the sphere. The standard monopore case is obtained as a particular solution.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Heat and mass transfer 18 (1984), S. 43-48 
    ISSN: 1432-1181
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Description / Table of Contents: Zusammenfassung Es wird die exakte analytische Lösung für den allgemeinen Fall der instationären Stoffübertragung zwischen einem Festkörper mit biporöser Struktur (bestehend aus einer Mikro- und einer Makroporosität) und dem äußeren Fluid vorgestellt. Der Transport in dem Feststoff erfolgt mittels molekularer Diffusion. Außerhalb der Feststoffpartikel wird der konvektive Filmwiderstand berücksichtigt. Eine allgemeine Formel wird angegeben, die für die unendliche Platte, für den unendlichen Zylinder und für die Kugel anwendbar ist. Die Lösung für das übliche monopore Modell ergibt sich als Sonderfall.
    Notes: Abstract This paper presents the exact analytical solution for the general case of transient mass transfer between a solid with a biporous structure (with a micro and a macroporosity) and the entouring finite fluid. The transport inside the solid is by molecular diffusion and outside of it the convective film resistance is included. A general expression is given which is valid for the infinite plate, for the infinite cylinder and for the sphere. The standard monopore case is obtained as a particular solution.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recently it was demonstrated that sprouting of dopaminergic neurons and a microglial and astrocyte response follows both partial lesions of the substantia nigra pars compacta and blockade of the D2 dopamine receptor. We therefore studied the effects of the combination of these two treatments (lesioning and D2 dopamine receptor blockade). Haloperidol administration caused a 57% increase in dopaminergic terminal tree size (measured as terminal density per substantia nigra pars compacta neuron) and an increase of glia in the striatum. Following small to medium nigral lesions (less than 60%), terminal tree size increased by 51% on average and returned density of dopaminergic terminals to normal. In contrast, administration of haloperidol for 16 weeks following lesioning resulted in reduced dopaminergic terminal density and terminal tree size (13%), consistent with absent or impaired sprouting. Glial cell numbers increased but were less than with lesions alone. When haloperidol was administered after the striatum had been reinnervated through sprouting (16–32 weeks after lesioning), terminal tree size increased up to 150%, similar to the effect of haloperidol in normal animals. By examining the effect of administering haloperidol at varying times following a lesion, we concluded that a switch in the effect of D2 dopamine receptor blockade occurred after dopaminergic synapses began to form in the striatum. We postulate that when synapses are present, D2 dopamine receptor blockade results in increased terminal density, whereas prior to synapse formation D2 dopamine receptor blockade causes attenuation of a sprouting response. We speculate that D2 dopamine receptors located on growth cones ‘push’ neurites toward their targets, and blockade of these receptors could lead to attenuation of sprouting.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previously we described the extent of sprouting that axons of the rat substantia nigra pars compacta (SNpc) undergo to grow new synapses and re-innervate the dorsal striatum 16 weeks after partial lesions. Here we provide insights into the timing of events related to the re-innervation of the dorsal striatum by regenerating dopaminergic nigrostriatal axons over a 104-week period after partial SNpc lesioning. Density of dopamine transporter and tyrosine hydroxylase immunoreactive axonal varicosities (terminals) decreased up to 80% 4 weeks after lesioning but returned to normal by 16 weeks, unless SNpc lesions were greater than 75%. Neuronal tracer injections into the SNpc revealed a 119% increase in axon fibres (4 mm rostral to the SNpc) along the medial forebrain bundle 4 weeks after lesioning. SNpc cells underwent phenotypic changes. Four weeks after lesioning the proportion of SNpc neurons that expressed tyrosine hydroxylase fell from 90% to 38% but returned to 78% by 32 weeks. We discuss these phenotype changes in the context of neurogenesis. Significant reductions in dopamine levels in rats with medium (30–75%) lesions returned to normal by 16 weeks whereas recovery was not observed if lesions were larger than 75%. Finally, rotational behaviour of animals in response to amphetamine was examined. The clear rightward turning bias observed after 2 weeks recovered by 16 weeks in animals with medium (30–75%) lesions but was still present when lesions were larger. These studies provide insights into the processes that regulate sprouting responses in the central nervous system following injury.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...