TH protein and mRNA in nigrostriatal dopaminergic neurons are down-regulated by continuous but not intermittent apomorphine

Iwata, S.; Nomoto, Masahiro; Kaseda, Shun; Tanoue, Shiroh; Shimosaka, Misako; Fukuda, Takeo

doi:10.1016/s0169-328x(00)00182-0

Cited by 11 publications

(8 citation statements)

References 15 publications

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“…Already reported increases in dopamine turnover following GDNF delivery might be therefore due to increased cofactor production (Hudson et al 1995;Georgievska et al 2004). In turn, chronically elevated striatal dopamine levels and dopamine receptor stimulation results in down-regulation of TH-mRNA (Iwata et al 2000), as negative feedback control to normalize the dopaminergic input in this highly regulated system. Strikingly, dopamine levels in our study were significantly decreased, suggesting either a rather slow adaptation of the system with transient overcompensation or involvement of a more direct regulation of TH transcription and pterine biosynthesis through distinct GDNF signaling pathways, irrespective of striatal neurotransmitter levels.…”

Section: Discussionmentioning

confidence: 99%

“…2004). In turn, chronically elevated striatal dopamine levels and dopamine receptor stimulation results in down‐regulation of TH‐mRNA (Iwata et al . 2000), as negative feedback control to normalize the dopaminergic input in this highly regulated system.…”

Section: Discussionmentioning

confidence: 99%

“…2004). It has been proposed that the initial GDNF‐mediated dopamine turnover increase might lead to compensatory down‐regulation of TH gene expression, a mechanism observed after chronic activation of dopamine receptors stimulated by the dopamine agonist apomorphin (Iwata et al . 2000).…”

mentioning

confidence: 99%

“…However, other recent studies have shown that long-term GDNF overexpression in the intact nigrostriatal pathway induces a down-regulation of tyrosine hydroxylase (TH) in dopaminergic neurons (Rosenblad et al 2003;Georgievska et al 2004). It has been proposed that the initial GDNF-mediated dopamine turnover increase might lead to compensatory down-regulation of TH gene expression, a mechanism observed after chronic activation of dopamine receptors stimulated by the dopamine agonist apomorphin (Iwata et al 2000). In addition to the observed TH down-regulation, however, the effect of GDNF overexpression on other enzymes of dopamine biosynthesis has not yet been investigated.…”

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confidence: 99%

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Long‐term glial cell line‐derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production

Sajadi

Bauer

Thöny

et al. 2005

Journal of Neurochemistry

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Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic system. Brain delivery of glial cell line-derived neurotrophic factor (GDNF) has been shown to protect and restore the dopaminergic pathway in various animal models of PD. However, GDNF overexpression in the dopaminergic pathway leads to a timedependent down-regulation of tyrosine hydroxylase (TH), a key enzyme in dopamine synthesis. In order to elucidate GDNF-mediated biochemical effects on dopaminergic neurons, we overexpressed GDNF in the intact rat striatum using a lentiviral vector-mediated gene transfer technique. Longterm GDNF overexpression led to increased GTP cyclohydrolase I (GTPCH I) activity and tetrahydrobiopterin (BH 4 ) levels. Further, we observed a down-regulation of TH enzyme activity in morphologically intact striatal dopaminergic nerve terminals, as well as a significant decrease of dopamine levels in striatal tissue samples. These results indicate that longterm GDNF delivery is a major factor affecting dopamine biosynthesis via a direct or indirect modulation of TH and GTPCH I and further underscore the importance of assessing both GDNF dose and delivery duration prior to clinical application in order to circumvent potentially adverse pharmacological effects on the biosynthesis of dopamine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Long‐term glial cell line‐derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production

Sajadi

Bauer

Thöny

et al. 2005

Journal of Neurochemistry

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“…One possibility is that greater levels of TH expression are associated with greater levels of catecholamine synthesis, and, in some instances, individual differences or genetic or pharmacological manipulations that result in differences in TH cell number also result in lower levels of dopamine synthesis and release in rats and mice (Baker et al, 1980(Baker et al, , 1982Sved et al, 1984;Iwata et al, 2000;Althini et al, 2003). For example, strain differences in mice in the number of TH-ir cells in the SNpc are correlated with differences in the level of dopamine synthesis and turnover in the striatum (Baker et al, 1980(Baker et al, , 1982Sved et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Tyrosine hydroxylase expression is affected by sexual vigor and social environment in male Cnemidophorus inornatus

Woolley

Sakata

Crews

2004

J of Comparative Neurology

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Although the distribution of catecholamine-synthesizing cells has been described for a variety of taxa, less is known about the functional significance of particular populations in nonmammalian species, especially reptiles. To understand the role of these populations in the display of social behaviors in lizards, we studied the interactive effects of sexual vigor (sexually vigorous vs. sluggish) and social condition (housing in isolation vs. with females) on the number and somal areas of cells expressing tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine synthesis, in male whiptail lizards, Cnemidophorus inornatus. We found that, regardless of social condition, sexually vigorous males had more TH-immunoreactive (TH-ir) cells in the dorsal hypothalamus (DH) relative to sluggish males. Sexually vigorous males also had more TH-ir cells in the substantia nigra pars compacta (SNpc), but this difference was significant only among males housed with females. Sexually vigorous males that had been housed with females had smaller TH-ir cells in the preoptic area (POA) than vigorous males housed in isolation. On the other hand, no significant differences were found in the anterior hypothalamus. These results highlight the regional heterogeneity in the plasticity of TH expression and suggest that, just as in other species, the DH, SNpc, and POA might be involved in the expression of social behaviors and in behavioral plasticity following social experiences in lizards.

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Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice

Iwata

Morioka

Iwabuchi

et al. 2005

Synapse

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In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.

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TH protein and mRNA in nigrostriatal dopaminergic neurons are down-regulated by continuous but not intermittent apomorphine

Cited by 11 publications

References 15 publications

Long‐term glial cell line‐derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production

Long‐term glial cell line‐derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production

Tyrosine hydroxylase expression is affected by sexual vigor and social environment in male Cnemidophorus inornatus

Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice

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