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  • 1
    Electronic Resource
    Electronic Resource
    Comparison of huntingtin proteolytic fragments in human lymphoblast cell lines and human brain (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Proteolytic fragments of huntingtin (htt) in human lymphoblast cell lines from HD and control cases were compared to those in human HD striatal and cortical brain regions, by western blots with epitope-specific antibodies. HD lymphoblast cell lines were heterozygous and homozygous for the expanded CAG triplet repeat mutations, which represented adult onset and juvenile HD. Lymphoblasts contained NH2- and COOH-terminal htt fragments of 20–100 kDa, with many similar htt fragments in HD compared to control lymphoblast cell lines. Detection of htt fragments in a homozygous HD lymphoblast cell line demonstrated proteolysis of mutant htt. It was of interest that adult HD lymphoblasts showed a 63–64 kDa htt fragment detected by the NH2-domain antibody, which was not found in controls. In addition, control and HD heterozygous cells showed a common 60–61 kDa band (detected by the NH2-domain antibody), which was absent in homozygous HD lymphoblast cells. These results suggest that the 63–64 kDa and 60–61 kDa NH2-domain htt fragments may be associated with mutant and normal htt, respectively. In juvenile HD lymphoblasts, the presence of a 66-kDa, instead of the 63–64 kDa N-domain htt fragment, may be consistent with the larger polyglutamine expansion of mutant htt in the juvenile case of HD. Lymphoblasts and striatal or cortical regions from HD brains showed similarities and differences in NH2- and COOH-terminal htt fragments. HD striatum showed elevated levels of 50 and 45 kDa NH2-terminal htt fragments [detected with anti(1–17) serum] compared to controls. Cortex from HD and control brains showed similar NH2-terminal htt fragments of 50, 43, 40, and 20 kDa; lymphoblasts also showed NH2-terminal htt fragments of 50, 43, 40, and 20 kDa. In addition, a 48-kDa COOH-terminal htt band was elevated in HD striatum, which was also detected in lymphoblasts. Overall, results demonstrate that mutant and normal htt undergo extensive proteolysis in lymphoblast cell lines, with similarities and differences compared to htt fragments observed in HD striatal and cortical brain regions. These data for in vivo proteolysis of htt are consistent with the observed neurotoxicity of recombinant NH2-terminal mutant htt fragments expressed in transgenic mice and in transfected cell lines that may be related to the pathogenesis of HD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.00940.x
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  • 2
    Electronic Resource
    Electronic Resource
    Regulation of μ-Opioid Receptor mRNA in Rat Globus Pallidus: Effects of Enkephalin Increases Induced by Short- and Long-Term Haloperidol Administration (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 63 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The mRNA encoding μ-opioid receptors is expressed in neurons of the globus pallidus, a region of the basal ganglia that receives a dense enkephalinergic innervation from the striatum. The regulation of the mRNAs encoding the opioid peptide enkephalin in the striatum and the μ-opioid receptor in the globus pallidus was examined with in situ hybridization histochemistry following short- or long-term haloperidol treatments, which alter striatal enkephalin mRNA levels. Animals were administered haloperidol daily for 3 or 7 days (1 mg/kg, s.c.) or continuously for 8 months (1 mg/kg, depot followed by oral). Enkephalin and μ-opioid receptor mRNA levels were unchanged after 3 days of haloperidol treatment. In contrast, the enkephalin mRNA level was increased in the striatum, and μ-opioid receptor mRNA levels were markedly decreased in the globus pallidus after 7 days of haloperidol administration. Similar effects were observed in rats treated with haloperidol for 8 months. The results provide the first evidence of regulation of μ-opioid receptor mRNA in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.63020777.x
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  • 3
    Electronic Resource
    Electronic Resource
    Energetic Dysfunction in Quinolinic Acid-Lesioned Rat Striatum (1997)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 69 (1997), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Impairment of mitochondrial energy metabolism may contribute to the selective neuronal degeneration observed in Huntington's disease and other neurodegenerative disorders. Intrastriatal injection of the excitotoxin, quinolinic acid, produces a pattern of neuronal death similar to that seen in Huntington's disease. However, little is known about the effects of quinolinic acid on striatal energetics. In the present work, time-dependent changes in energy metabolism caused by injection of quinolinic acid into rat striatum were examined. Oxygen consumption by free and synaptic mitochondria was quantified and correlated with the concentrations of nucleotides and amino acids at different times after injection. Compared with saline-treated controls, a decrease in ADP-stimulated (state 3) to basal (state 4) oxygen consumption (respiratory control ratio) by free mitochondria was apparent in quinolinic acid-injected striata as early as 6 h after treatment. No significant changes were seen in nucleotide concentrations at this time. By 12 h after injection, the decline in the respiratory control ratio was more pronounced (45%), and reductions in ATP, NAD, aspartate, and glutamate (30–60%) were also observed. These results show that injection of quinolinic acid in vivo produces progressive mitochondrial dysfunction, which may be a common and critical event in the cell death cascade initiated in Huntington's disease and in animal models of this neurodegenerative disorder. The indicators of mitochondrial function examined in this study, therefore, may be useful in evaluating the efficacy of neuroprotective agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1997.69041629.x
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  • 4
    Electronic Resource
    Electronic Resource
    Striatal Dopamine Release In Vitro: A β-Adrenoceptor-Regulated Response Not Mediated Through Cyclic AMP (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of (-)isoproterenol(106 M), dibutyryl cyclic AMP (10−2 M), and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (10−4 M) on in vitvo [3H]dopamine ([3H]DA) cllux and synthesis were studied in rat striatal slices continuously superfused with [3H]tyrosine. The β-adrenoceptor agonist (-)isoproterenol induced an immediate and significant facilitation of [3H]DA efflux but did not alter [3H]DA synthesis as measured by [3H]H2O formation. In contrast, both dibutyryl cyclic AMP and IBMX enhanced [3H]DA synthesis as well as efflux. The presence of IBMX in the superfusing medium did not potentiate the augmentation of [3H]DA efflux caused by (-)isoproterenol. Additionally, the blockade of [3H]DA synthesis by α-methyl-p-tyrosine (10−1 M) completely prevented the action of dibutyryl cyclic AMP on [3H]DA efflux. However, under similar conditions, (-)so proterenol was still able to increase [3H]DA efflux. The results suggest that (-)isoproterenol can modify striatal DA release through a mechanism not involving cyclic AMP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1982.tb11485.x
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  • 5
    Electronic Resource
    Electronic Resource
    Functional and molecular development of striatal fast-spiking GABAergic interneurons and their cortical inputs (2005)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 22 (2005), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Despite their small number, fast-spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed-forward inhibition of striatal medium-sized spiny (MS) projection neurons. We have examined the functional development of FS interneurons and their cortical inputs, and the expression of three of their molecular markers, in the dorsolateral rat striatum between postnatal days (P)12–14 and 19–23, the time of major corticostriatal synaptogenesis. FS interneurons were visualized with infrared differential interference contrast (IR-DIC) optics and examined with current-clamp recording in the presence of the GABAA receptor antagonist bicuculline methiodide. FS interneurons displayed action potentials at relatively high frequencies in response to depolarizing current pulses by P12, but developmental changes occurred in action potential and afterhyperpolarization duration and amplitude and input resistance between P12–14 and P19–23, as well as an increase in maximum firing frequency in response to depolarizing current pulses. Maturation in electrophysiological properties was paralleled by increases in Kv3.1 and parvalbumin mRNA expression, while GAD-67 mRNA levels remained constant. Furthermore, FS interneurons in the younger age group responded to stimulation of cortical afferents with excitatory postsynaptic potentials (EPSPs) of higher amplitudes and received significantly more spontaneous depolarizing inputs than did MS neurons. Thus, FS interneurons are under frequent and continuous cortical influence by the end of the 2nd postnatal week, a time when corticostriatal synapses are sparse, suggesting that they may provide a major inhibitory influence in the striatum during the period of intense developmental maturation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2005.04303.x
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  • 6
    Electronic Resource
    Electronic Resource
    In situ hybridization of mRNA for β-preprotachykinin and preprosomatostatin in adult rat dorsal root ganglia: comparison with immunocytochemical localization (1988)
    Springer
    Journal of neurocytology 17 (1988), S. 671-681 
    Details
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry was used to identify neurons in rat dorsal root ganglia that contained mRNAs encoding β-preprotachykinin and preprosomatostatin. The distribution of these neurons was compared with the distribution of neurons containing tachykinins or somatostatin, identified using immunocytochemical techniques. Neurons labelled for β-preprotachykinin mRNA constituted 20% of the total neuronal population and belonged to the small cell class. Neurons labelled for preprosomatostatin mRNA with either RNA or DNA hybridization probes constituted approximately 10% of the total cells and comprised a small cell group that differed in average size from the β-preprotachykinin labelled population. The distribution of cells containing tachykinin- or somatostatin-like immunoreactive material was identical to the distribution of cells containing the respective mRNAs and, in addition, individual somata in adjacent sections contained both the mRNA precursor and the peptide. These results suggest that for these neuropeptides the sensitivity of the two methods is equivalent and the respective mRNAs and peptides are co-localized in the same neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01260994
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  • 7
    Electronic Resource
    Electronic Resource
    Heterogeneous distribution of dopamine D2 receptor mRNA in the rat striatum: A quantitative analysis with in situ hybridization histochemistry (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 231 (1991), S. 548-558 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Dopamine D2 receptor mRNAs have recently been cloned and their gross distribution in the central nervous system described. Quantitative in situ hybridization histochemistry with a cRNA probe complementary to the mRNAs encoding approximately 70% of the third intracellular loop of the rat D2 receptor was performed on sections of rat brain to determine whether differences previously observed in the density of ligand binding sites in subregions of the striatum were related to differences in mRNA levels. Film autoradiographic analysis demonstrated 30% more hybridization signal in the lateral compared to the medial caudate-putamen, a distribution parallel to that of binding of ligands specific for the D2 receptor. Inspection at the cellular level using emulsion autoradiography also indicated a differential distribution of the D2 receptor mRNA. Fewer positively labelled cells, as well as fewer silver grains per cell, were seen in the medial compared to the lateral half of the striatum. This suggests that the gradient seen in autoradiographic studies of the distribution of D2 receptors is related both to regional differences in D2 mRNA levels and to the density of cells expressing the receptor. In addition, the distribution of cells expressing D2 receptor mRNA in the extrastriosomal matrix was compared to that in striosomes identified by the presence of a high density of 3H-naloxone binding sites. Labelled cells were mainly found in the matrix (3H-naloxone binding-poor) but were also seen in striosomes (3H-naloxone binding-rich). The results suggest that differences in levels of D2 binding sites in subregions of the striatum are related to differences in the level of expression of this receptor in intrinsic striatal neurons, suggesting differential regulation of dopamine D2 receptor gene expression in topographically distinct striatal neurons.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092310416
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