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1.
Dopamine antagonist haloperidol decreases substance P, substance K, and preprotachykinin mRNAs in rat striatonigral neurons 总被引:5,自引:0,他引:5
M J Bannon J M Lee P Giraud A Young H U Affolter T I Bonner 《The Journal of biological chemistry》1986,261(15):6640-6642
Rat genomic clones were used to quantitate preprotachykinin mRNAs in the rat basal ganglia, while the tachykinin peptide products substance P and substance K were measured by radioimmunoassay. Administration of the dopamine antagonist (antipsychotic) drug haloperidol significantly decreased substance P, substance K, and both alpha (substance P encoding) and beta (substance P/substance K encoding) preprotachykinin mRNAs, suggesting a drug-induced decrease in striatonigral tachykinin biosynthesis. The time course for decreased preprotachykinin mRNAs and tachykinins apparently parallels the period of maximum risk for the development of certain antipsychotic drug-induced extrapyramidal side effects seen clinically. Tachykinin interaction with dopamine neurons may play an important role in the modulation of basal ganglia function. 相似文献
2.
The distribution of hydroxyproline-rich glycoprotein (HRGP) mRNAs in the shoots of dark-grown and irradiated cucumber ( Cucumis sativus L. cv. Burpee pickler) and pea ( Pisum sativum L. cv. Alaska) was studied. A cloned genomic DNA fragment encoding carrot ( Daucus carota ) root extensin (pDC5A1) was used to measure HRGP mRNAs from cucumber and pea along the length of dark-grown and irradiated shoots. There was a marked difference in the levels of HRGP mRNAs isolated from apical and basal regions of cucumber. Whereas apical, elongating regions had low levels of HRGP mRNAs, basal regions of the shoot had high levels. Levels of HRGP mRNAs were also compared in shoots of dark-grown and irradiated cucumber. Although light inhibits hypocotyl growth, it had no effect on levels of HRGP mRNAs. There was no gradient in the distribution of HRGP mRNAs along the epicotyl of dark-grown pea. As was the case with cucumber, light did not affect the accumulation of HRGP mRNAs in pea shoots. We conclude that light does not affect elongation by regulating the accumulation of HRGP mRNAs. The gradient of accumulation of HRGP mRNAs along the hypocotyl of cucumber probably reflects differences in cellular differentiation along the shoot. 相似文献
3.
The use ofin situ hybridization histochemistry for the study of neuropeptide gene expression in the human brain 总被引:2,自引:0,他引:2
1. The application of in situ hybridization histochemistry to the study of neuropeptide gene expression in human brain postmortem tissues is reviewed. We focus on neuropeptides preferentially expressed in hypothalamus and basal ganglia. 32P-labeled oligonucleotides were used as hybridization probes. 2. Autoradiography combined with computerized image analysis was used to visualize and quantify the hybridization signal. 3. Several criteria were considered in order to ascertain the specificity of the signal, including Northern analysis, use of heterologous probes, competition assays, and thermal stability of the hybrids. 4. In control human striatum high levels of hybridization signal were observed for somatostatin, neuropeptide Y, and preproenkephalin A mRNAs. In contrast, no detectable signal was observed with the cholecystokinin, arginine-vasopressin, and oxytocin probes in this area. In the hypothalamus high levels of oxytocin and arginine-vasopressin mRNAs were visualized in several nuclei. Preproenkephalin A and somatostatin mRNAs were also observed in this region, while cholecystokinin mRNA was not detected. 5. No significant correlations were found between the density of the hybridization signal and parameters such as postmortem delay, age, and gender in the population studied. 6. Finally, alterations of mRNA levels for some of these peptides were found in Parkinson's disease and Huntington's chorea striatal tissues. 7. These results show that in situ hybridization histochemistry can be used to examine at the microscopic level neuropeptide gene expression in postmortem materials. 相似文献
4.
Périer C Marin C Jimenez A Bonastre M Tolosa E Hirsch EC 《Journal of neurochemistry》2003,86(6):1328-1337
Inactivation of the subthalamic nucleus (STN) or the internal segment of the pallidum (GPi)/entopeduncular nucleus (EP) by deep brain stimulation or lesioning alleviates clinical manifestations of Parkinson's disease (PD) as well as reducing the side-effects of levodopa treatment. However, the effects of STN or entopeduncular nucleus (EP) lesion on levodopa-related motor fluctuations and on neurochemical changes induced by levodopa remain largely unknown. The effects of such lesions on levodopa-induced motor alterations were studied in 6-hydroxydopamine (6-OHDA)-lesioned rats and were assessed neurochemically by analyzing the functional activity of the basal ganglia nuclei, using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase as molecular markers of neuronal activity. At the striatal level, preproenkephalin (PPE) mRNA levels were analyzed. We found in 6-OHDA-lesioned rats that a unilateral STN or EP lesion ipsilateral to the 6-OHDA lesion had no effect on either the shortening in the duration of the levodopa-induced rotational response or the levodopa-induced biochemical changes in the basal ganglia nuclei. In contrast, overexpression of PPE mRNA due to levodopa treatment was reversed by the STN or EP lesion. Our study thus shows that lesion of the EP or STN may counteract some of the neurochemical changes induced by levodopa treatment within the striatum. 相似文献
5.
Illumination of maize roots initiates changes in mRNA levels and in the activities of proteins within the root cap. Using Northern analysis we showed a 5–6-fold increase in the levels of three specific mRNAs and a 14-fold increase in plastid mRNA. This increase is rapid, occurring within 30 minutes of illumination. With prolonged periods of darkness following illumination, messages return to levels observed in dark, control caps. For two species of mRNA illumination results in a reduction in message levels. Light-stimulated increases in the levels of specific mRNAs are proportionally greater than are increases in the activities of corresponding proteins. We suggest that the light-stimulated increase in protein activity in root caps may be preceded by and occur as a consequence of enhanced levels of mRNA. Our work suggests that photomorphogenesis in roots could involve changes in the levels of a wide variety of mRNAs within the root cap. 相似文献
6.
Gourfinkel-An I Vila M Faucheux B Duyckaerts C Viallet F Hauw JJ Brice A Agid Y Hirsch EC 《Journal of neurochemistry》2002,80(3):466-476
On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization. 相似文献
7.
† Marcelle Morrison-Bogorad Anton L. Zimmerman Sibile Pardue 《Journal of neurochemistry》1995,64(1):235-246
Abstract: Systematic review of antemortem clinical information on randomly selected Alzheimer disease (AD) patients revealed that ∼40% of the patients had a recorded fever of ≥39.2°C at or near death. Using isolation and quantitation techniques appropriate for analysis of human brain mRNAs, we found that low levels of inducible heat-shock protein 70 (hsp70) mRNAs were present in cerebellum of afebrile AD patients and that mRNA levels were usually lower in two brain regions affected in AD, i.e., hippocampus and temporal cortex. Levels of hsp70 mRNAs were increased three- to 33-fold in cerebellum of febrile patients compared with levels in patients whose recorded temperatures were ≤37.5°C. Levels of hsp70 mRNAs were also increased in hippocampus and cortex of these febrile patients, but to a lesser extent than cerebellum. Heat-shock cognate 70 (hsc70) mRNAs were present at highest levels in afebrile cerebellum and were also present in the other brain regions. In cerebellum of patients with the highest temperatures, hsc70 mRNAs were induced severalfold over basal levels. Although there was a low and variable induction of hsc70 mRNAs in temporal cortex of these patients, there was no evidence for any induction in hippocampus. Increased heat-shock 70 mRNA levels did not correlate with hypoxia, coma, hypertension, hypoglycemia, seizures, or medication. These results indicate that a specific agonal stress, namely fever, can increase the levels of heat shock 70 mRNAs in AD brain; however, there is no evidence to suggest that affected regions of AD brain have higher overall levels of these mRNAs. Failure to obtain adequate agonal state information could result in inaccurately identifying short-term stress-related changes in postmortem brain as neuropathology characteristic of a chronic disease state. 相似文献
8.
The effects of subculture of tissue cultures on the levels of certain mRNAs have been investigated, and the action of cytokinins on the disposition of certain mRNAs between possible non-translating and translating pools has been determined. mRNA preparations were assayed by cell free translation with message-dependent reticulocyte lysate and the in vitro products resolved by polyacrylamide gel electrophoresis. Subculture of the cells caused a rapid stimulation of polysome formation. It also increased the translatable levels of a small group of mRNAs, one of which was present in both bean and soybean cultures. Cytokinins caused a slight increase in polysome levels after subculture, but had no effect on the levels of particular mRNAs, nor on the distribution of mRNAs between a non-translating and translating pool, nor on polysome levels in the absence of subculture.Abbreviations EDTA
ethylenediaminetetra acetic acid
- EGTA
1,2-di-(2-aminoethoxy)ethane-NNNN-tetra acetic acid
- IEF
isoelectric focusing
- SDS
sodium dodecyl sulphate 相似文献
9.
10.
Miquel Vila Concepció Marin Merle Ruberg Anna Jimenez Rita Raisman-Vozari Yves Agid Eduardo Tolosa Etienne C. Hirsch 《Journal of neurochemistry》1999,73(1):344-352
In Parkinson's disease, nigrostriatal denervation leads to an overactivity of the subthalamic nucleus and its target areas, which is responsible of the clinical manifestations of the disease. Because the subthalamic nucleus uses glutamate as neurotransmitter and is innervated by glutamatergic fibers, pharmacological blockade of glutamate transmission might be expected to restore the cascade of neurochemical changes induced by a dopaminergic denervation within the basal ganglia. To test this hypothesis, two types of glutamate antagonists, the NMDA receptor antagonist MK-801 and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist LY293558, were administered systemically, either alone or in combination with L-DOPA, in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. The effect of treatment was assessed neurochemically by analyzing at the cellular level the functional activity of basal ganglia output structures and the subthalamic nucleus using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase, respectively, as molecular markers of neuronal activity. The present study shows that treatment with glutamate antagonists, and particularly with AMPA antagonists, alone or in combination with L-DOPA, reverses the overactivity of the subthalamic nucleus and its target areas induced by nigrostriatal denervation. These results furnish the neurochemical basis for the potential use of glutamate antagonists as therapeutic agents in Parkinson's disease. 相似文献
11.
Jill M. Delfs Lei Yu †Gaylord D. Ellison Terry Reisine Marie-Françoise Chesselet 《Journal of neurochemistry》1994,63(2):777-780
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. 相似文献
12.
Mark L. Johnson Joseph Levy Jeffrey M. Rosen 《In vitro cellular & developmental biology. Plant》1985,21(8):439-444
Summary Milk protein gene expression was studied in cell subpopulations of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma cells enriched or depleted for casein production grown on attached collagen gels.
Culture of these cells in the presence of 10% fetal bovine serum, insulin (5 μg/ml), hydrocortisone (10 μg/ml), and prolactin
(5 μg/ml) maintained α-, β-, and γ-casein and whey acidic protein mRNAs at levels identical to cells isolated from perphenazine-treated
rats. Whey acidic protein mRNA levels in the tumor cells relative to the 14-d lactating gland were greater than those of the
casein mRNAs. Withdrawal of prolactin from the casein-producing cells resulted in the loss of all four milk protein mRNAs.
Subsequent addition of prolactin to the withdrawn cells caused a rapid accumulation of these mRNAs to prewithdrawal levels.
Milk protein gene expression in this tumor cell subpopulation is modulated by prolactin (in the presence of insulin and hydrocortisone)
in a similar manner to that observed in the normal mammary gland when these tumor cells are cultured on attached collagen
gels.
This work was supported by National Institutes of Health grant CA 16303. M. L. Johnson was the recipient of NIH Fellowship,
HD 06157. 相似文献
13.
The major anatomical characteristics of the main axis of the basal ganglia are: (1) Numerical reduction in the number of neurons across layers of the feed-forward network, (2) lateral inhibitory connections within the layers, and (3) neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia neurons and on the efficacy of information transmission along the basal ganglia axis. We recorded the simultaneous activity of neurons in the output stages of the basal ganglia as well as the activity of dopaminergic and cholinergic neurons during the performance of a probability decision-making task. We found that the functional messages of the cholinergic and dopaminergic neurons differ, and that the cholinergic message is less specific than that of the dopaminergic neurons. The output stage of the basal ganglia showed uncorrelated neuronal activity. We conclude that despite the huge numerical reduction from the cortex to the output nuclei of the basal ganglia, the activity of these nuclei represents an optimally compressed (uncorrelated) version of distinctive features of cortical information. 相似文献
14.
Sibile Pardue Anton L. Zimmerman Marcelle Morrison-Bogorad 《Cellular and molecular neurobiology》1994,14(4):341-357
Summary 1. Altered mRNA levels in postmortem brain tissue from persons with Alzheimer's disease (AD) or other neurological diseases are usually presumed to be characteristic of the disease state, even though both agonal state (the physiological state immediately premortem) and postmortem interval (PMI) (the time between death and harvesting the tissue) have the potential to affect levels of mRNAs measured in postmortem tissue. Although the possible effect of postmortem interval on mRNA levels has been more carefully evaluated than that of agonal state, many studies assume that all mRNAs have similar rates of degradation postmortem.2. To determine the postmortem stability of inducible heat shock protein 70 (hsp70) mRNAs, themselves unstablein vivo at normal body temperature, rats were heat shocked in order to induce synthesis of the hsp70 mRNAs. hsp70 mRNA levels in cerebellum and cortex were then compared to those of their heat shock cognate 70 (hsc70) mRNAs, as well as to levels of 18S rRNAs, at 0 and at 24 hr postmortem.3. Quantiation of northern blots after hybridization with an hsp70 mRNA-specific oligo probe indicated a massive loss of hsp70 mRNA signal in RNAs isolated from 24-hr postmortem brains; quantitation by slot-blot hybridization was 5- to 15-fold more efficient. Even using the latter technique, hsp70 mRNA levels were reduced by 59% in 24-hr-postmortem cerebellum and by 78% in cortex compared to mRNA levels in the same region of 0-hr-postmortem brain. There was little reduction postmortem in levels of the hsp70 mRNAs or of 18S rRNAs in either brain region.4.In situ hybridization analysis indicated that hsp70 mRNAs were less abundant in all major classes of cerebellar cells after 24 hr postmortem and mRNAs had degraded severalfold more rapidly in neurons than in glia. There was no corresponding loss of intracellular 18S rRNA in any cell type.5. We conclude from these results that the effect of postmortem interval on mRNA degradation must be carefully evaluated when analyzing levels of inducible hsp70 mRNAs, and perhaps other short-lived mRNAs, in human brain. 相似文献
15.
We propose to investigate brain electrophysiological alterations associated with Parkinson’s disease through a novel adaptive dynamical model of the network of the basal ganglia, the cortex and the thalamus. The model uniquely unifies the influence of dopamine in the regulation of the activity of all basal ganglia nuclei, the self-organised neuronal interdependent activity of basal ganglia-thalamo-cortical circuits and the generation of subcortical background oscillations. Variations in the amount of dopamine produced in the neurons of the substantia nigra pars compacta are key both in the onset of Parkinson’s disease and in the basal ganglia action selection. We model these dopamine-induced relationships, and Parkinsonian states are interpreted as spontaneous emergent behaviours associated with different rhythms of oscillatory activity patterns of the basal ganglia-thalamo-cortical network. These results are significant because: (1) the neural populations are built upon single-neuron models that have been robustly designed to have eletrophysiologically-realistic responses, and (2) our model distinctively links changes in the oscillatory activity in subcortical structures, dopamine levels in the basal ganglia and pathological synchronisation neuronal patterns compatible with Parkinsonian states, this still remains an open problem and is crucial to better understand the progression of the disease.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09653-y) contains supplementary material, which is available to authorized users. 相似文献
16.
R Sandyk 《Life sciences》1985,37(18):1655-1663
The endogenous opioid peptides have for some time been implicated in the regulation of motor behavior in animals. Recently, however, there is increased evidence to suggest a role for these peptides in the control of human motor functions as well as in the pathophysiology of abnormal movement disorders. Degeneration of opioid peptide-containing neurons in the basal ganglia has been demonstrated in Parkinson's disease and Huntington's chorea, but the clinical significance of these findings is largely unknown. On the other hand, there is evidence that excessive opioid activity may be important in the pathophysiology of some movement disorders such as tardive dyskinesia, progressive supra-nuclear palsy, and a subgroup of Tourette's patients. These findings indicate that diseases of the basal ganglia are possibly associated with alterations in opioid peptide activity, and that these alterations may be useful in designing experimental therapeutic strategies in these conditions. 相似文献
17.
Stephanie L. Moon John R. Anderson Yutaro Kumagai Carol J. Wilusz Shizuo Akira Alexander A. Khromykh Jeffrey Wilusz 《RNA (New York, N.Y.)》2012,18(11):2029-2040
All arthropod-borne flaviviruses generate a short noncoding RNA (sfRNA) from the viral 3′ untranslated region during infection due to stalling of the cellular 5′-to-3′ exonuclease XRN1. We show here that formation of sfRNA also inhibits XRN1 activity. Cells infected with Dengue or Kunjin viruses accumulate uncapped mRNAs, decay intermediates normally targeted by XRN1. XRN1 repression also resulted in the increased overall stability of cellular mRNAs in flavivirus-infected cells. Importantly, a mutant Kunjin virus that cannot form sfRNA but replicates to normal levels failed to affect host mRNA stability or XRN1 activity. Expression of sfRNA in the absence of viral infection demonstrated that sfRNA formation was directly responsible for the stabilization of cellular mRNAs. Finally, numerous cellular mRNAs were differentially expressed in an sfRNA-dependent fashion in a Kunjin virus infection. We conclude that flaviviruses incapacitate XRN1 during infection and dysregulate host mRNA stability as a result of sfRNA formation. 相似文献
18.
Tobacco genes encoding acidic and basic isoforms of pathogenesis-related proteins display different expression patterns 总被引:16,自引:0,他引:16
Johan Memelink Huub J. M. Linthorst Rob A. Schilperoort J. Harry C. Hoge 《Plant molecular biology》1990,14(2):119-126
The induction by cytokinin stress and ethylene of nine different tobacco mosaic virus-inducible mRNA classes (termed A-I) encoding pathogenesis-related (PR) proteins was studied. The induced mRNA levels were compared to basal levels in healthy tobacco plants grown in tissue culture and in a greenhouse. Cytokinin stress and ethylene were found to induce different subsets of the mRNAs, indicating that ethylene is not the primary inducing signal in cytokinin-stressed shoots. mRNAs F, H and G encoding the basic hydrolytic enzymes chitinase, -1,3-glucanase and a basic equivalent of PR-1, respectively, were found to be expressed at high levels in roots of healthy plants. mRNAs D, I and B encoding the acidic equivalents of the proteins proved to be present at low levels in healthy plants. These results indicate that genes encoding basic and acidic isoforms of pathogenesis-related proteins are differentially regulated. 相似文献
19.
Stefano GB Mantione K Jones D Zhu W Casares F Cadet P 《Neuro endocrinology letters》2004,25(1-2):57-61
Pedal ganglia excised and maintained in culture for up to 2 h, release NO at low levels. The range can vary between 0 to 1.1 nM. Non-stimulated immunocytes do not significantly stimulate ganglionic NO release when incubated with pedal ganglia. However, ganglia exposed to immunocytes that had been previously activated by a 30 min incubation with interleukin 1 beta, release NO significantly above basal levels. In these experiments, 91 +/- 2.5% of the non-stimulated immunocytes exhibited form factors in the 0.72 to 0.89 range (sampled prior to ganglionic addition), whereas 62 +/- 10.3% of the interleukin 1 beta stimulated immunocytes had form factors in the 0.39 to 0.49 range, demonstrating activation. Addition of the nitric oxide synthase inhibitor, L-NAME (10(-4) M), inhibited basal ganglionic NO release as well as that initiated by exposing the ganglia to activated immunocytes. Interestingly, non activated immunocytes, following ganglionic exposure, exhibited activity levels in the 13% range, representing a non significant increase. Cells exposed to interleukin 1 beta had a 65% activity level at the beginning of the experiment, followed by a drop of activity to 19 +/- 3.2% after ganglionic exposure. Repeating this last observation in the presence of L-NAME (10(-4) M), brought the activity level of the immunocytes back to the pre-ganglionic exposure level of activity, demonstrating that ganglionic NO was involved in down regulating immunocyte activity. 相似文献
20.
John J. Harada Catherine S. Baden Lucio Comai 《Molecular & general genetics : MGG》1988,212(3):466-473
Summary We investigated the control of genes expressed primarily during seed germination and postgerminative development in Brassica napus L. We identified cloned mRNA sequences which became prevalent within 1 day after the start of imbibition and were at low or undetectable levels in immature embryos, dry seeds, and leaves. Most postgermination-abundant mRNAs accumulated primarily, though not exclusively, in different parts of the seedling. Of the 14 cloned mRNAs, 8 were prevalent in cotyledons, 2 were abundant in seedling axes, and 4 were approximately equally distributed in both parts. We showed that although these mRNAs reached maximal levels in seedlings, the spatially regulated mRNAs were also detected at distinct embryonic stages; mRNAs prevalent in seedling axes accumulated primarily during early embryogenesis while cotyledon-abundant mRNA concentration increased during late embryogeny. We conclude that the temporal and spatial regulation of gene expression in seedlings reflects similarities and differences in the physiological functions of cotyledons and axes. Furthermore, the regulated expression of cotyledon-abundant genes during late embryogeny suggests that the mRNAs and possibly proteins may accumulate in preparation for subsequent seedling growth. Similarities in the accumulation of cotyledon-abundant mRNAs may indicate coordinate regulation of this gene set.Abbreviations DAF
days after flowering
- DAI
days after the start of imbibition
- HAI
hours after the start of imbibition
- kb
kilobase(pairs) 相似文献