Neuronal Dopamine Subpopulations Maintained in Hypothalamic Slice Explant Cultures Exhibit Distinct Tyrosine Hydroxylase mRNA Turnover Rates

Maurer, Jennifer A.; Wray, Susan

doi:10.1523/jneurosci.17-12-04552.1997

Cited by 21 publications

(16 citation statements)

References 52 publications

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“…However, mRNA levels found in dams whose pups were permanently removed did rise to higher levels than in dams that received their pups back. In theory, we expected the decline in TH mRNA in pup-returned dams to levels of continuously suckling dams with time, based on the 6-h half-life described for TH mRNA (Maurer and Wray 1997). Our observation indicates that resuckling alters the stability of the TH mRNA producing machinery after being awakened by removal of pups.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Temporal Programs Regulating Tyrosine Hydroxylase and Enkephalin Expressions in TIDA Neurons of Lactating Rats Following Pup Removal and then Pup Return

Szabó

Snyder

et al. 2010

J Mol Neurosci

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Dopamine (DA) and enkephalin (ENK) release from the tuberoinfundibular dopaminergic neurons (TIDA) into the hypophysial portal circulation is fundamentally different under non-lactating and lactating conditions. The aim of this experiment was to compare the effect of a brief interruption then resumption of suckling on the temporal program of tyrosine hydroxylase (TH; rate-limiting enzyme of dopamine synthesis) and ENK regulation in dams. On post partum day 10, pups were removed for a 4-h period from a group of the dams then returned for 4-and 24-h periods. It was examined whether such a brief interruption of suckling provokes full up-regulation of TH and down-regulation of ENK, and whether reinitiation of suckling limits the extent to which TH upand ENK down-regulate. At the end of experiment, the animals were decapitated. In situ hybridization was used to examine the expression of TH and ENK mRNA in the arcuate nucleus where TIDA neurons reside. The results showed that, on one hand, the removal of pups induced TH up-regulation, on the other hand, ENK expression also increased 8 h after removal of pups and then started to slowly decline. In dams whose sucklings were reinitiated both TH and ENK mRNAs were up-regulated at least for a day. ENK expression responded more slowly to the removal of pups than expression of TH, and after reinitiation of suckling, the temporal program of regulation of both TH and ENK expressions ran parallel in the first 24 h.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Temporal Programs Regulating Tyrosine Hydroxylase and Enkephalin Expressions in TIDA Neurons of Lactating Rats Following Pup Removal and then Pup Return

Szabó

Snyder

et al. 2010

J Mol Neurosci

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“…A recent study demonstrated substantial differences in basal TH mRNA turnover rates between different neuronal populations from as short a time as 6 -7 h, in the dopaminergic neurons of the arcuate nucleus, to as long as 11-23 h, in the dopaminergic midhypothalamic neurons (4). In addition, TH mRNA is destabilized in the dopaminergic cells of the arcuate nucleus in a manner that corresponds to the rhythmic output displayed by these neurons (4).…”

mentioning

confidence: 99%

Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Paulding¹,

Czyzyk-Krzeska

1999

Journal of Biological Chemistry

128

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The stability of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, is regulated by oxygen tension in the pheochromocytomaderived PC12 cell line. We previously identified a pyrimidine-rich 27-base-long protein-binding sequence in the 3-untranslated region of TH mRNA that is associated with hypoxia-inducible formation of a ribonucleoprotein complex (hypoxia-inducible protein-binding site (HIPBS)). In this study, we show that HIPBS is an mRNA stabilizing element necessary for both constitutive and hypoxia-regulated stability of TH mRNA. The mutations within this sequence that abolish protein binding markedly decrease constitutive TH mRNA stability and ablate its hypoxic regulation. A short fragment of TH mRNA that contains the wild-type HIPBS confers the increased mRNA stability to the reporter chloramphenicol acetyltransferase mRNA. However, it is not sufficient to confer hypoxic regulation. The HIPBS element binds two isoforms of a 40-kDa poly(C)-binding protein (PCBP). Hypoxia induces expression of the isoform 1, PCBP 1 , but not the isoform 2, PCBP 2 , in PC12 cells.Tyrosine hydroxylase (TH), 1 the rate-limiting enzyme in the biosynthesis of catecholamines, is expressed in specific populations of neurons in the central and peripheral nervous systems, in the neuroendocrine cells of the adrenal medulla and carotid body, and in cultured cell lines such as the pheochromocytomaderived PC12 cell line. Regulation of TH gene expression at the level of gene transcription is well documented. Recently, there has been growing evidence that TH mRNA is also regulated at the level of mRNA stability. TH mRNA is a stable message with a half-life that varies from 9 to 16 h in various subclones of PC12 cells (1-3). It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2). In contrast, the stability of TH mRNA does not change in PC12 cells during stimulation of TH mRNA expression by dexamethasone or forskolin (3). A recent study demonstrated substantial differences in basal TH mRNA turnover rates between different neuronal populations from as short a time as 6 -7 h, in the dopaminergic neurons of the arcuate nucleus, to as long as 11-23 h, in the dopaminergic midhypothalamic neurons (4). In addition, TH mRNA is destabilized in the dopaminergic cells of the arcuate nucleus in a manner that corresponds to the rhythmic output displayed by these neurons (4).Our laboratory demonstrated that hypoxia augments the stability of TH mRNA in PC12 cells (5). We identified a 27-base-long pyrimidine-rich sequence within the TH mRNA 3Ј-untranslated region (UTR) (1552-1578 bases of TH mRNA) that binds protein factors in a hypoxia-inducible manner (hypoxia-inducible protein-binding sequence (HIPBS)) in PC12 cells (6, 7), catecholaminergic cells of the superior cervical ganglia, and the dopaminergic cells of the carotid body (8). Mutational analysis revealed that the optimal protein-binding site is represented by the motif (U/C)(C/...

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“…The relatively rapid decrease of THir neurons after withdrawal of 9-me-BC might be attributed to the short half-life of TH mRNA, which has been reported to vary between 6 and 23 h in hypothalamic slice explant cultures [105]. Moreover, the half-life of the enzyme has been reported to be approximately 48 h in adrenal medulla [106].…”

Section: Mao-a and -B Inhibition [107]mentioning

confidence: 99%

Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug?

Polanski

Reichmann

Gille

2011

Expert Review of Neurotherapeutics

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β-carbolines are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). 9-methyl-β-carboline exhibits multimodal effects that could be beneficial in the treatment of PD. It shows stimulatory effects to dopaminergic neurons by increasing the expression of tyrosine hydroxylase and its transcription factors in pre-existing dopa decarboxylase immunoreactive neurons. Furthermore, 9-methyl-β-carboline has emerged as a substance with the rare property of a protective and regenerative/restorative potential for dopaminergic neurons by inducing gene expression of several neurotrophic factors and decreasing apoptotic cell signals. It reduces protein levels of α-synuclein and inhibits monoamine oxidase A and B. Finally, 9-methyl-β-carboline acts on multiple targets in the inflammatory cascade by inhibiting the proliferation of microglia, by decreasing chemotactic cytokines and by creating an anti-inflammatory environment in the CNS. This article summarizes our current knowledge of 9-methyl-carboline and discusses its potential role as a new drug for the treatment of PD.

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Neuronal Dopamine Subpopulations Maintained in Hypothalamic Slice Explant Cultures Exhibit Distinct Tyrosine Hydroxylase mRNA Turnover Rates

Cited by 21 publications

References 52 publications

Comparison of the Temporal Programs Regulating Tyrosine Hydroxylase and Enkephalin Expressions in TIDA Neurons of Lactating Rats Following Pup Removal and then Pup Return

Comparison of the Temporal Programs Regulating Tyrosine Hydroxylase and Enkephalin Expressions in TIDA Neurons of Lactating Rats Following Pup Removal and then Pup Return

Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug?

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