Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model rats and rats exposed to short- and long-term forced walking stress

Wang, Ping; Kitayama, Isao; Nomura, Junichi

doi:10.1016/s0024-3205(98)00183-0

Cited by 31 publications

(13 citation statements)

References 20 publications

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“…This has important implications for stress mediated behavior, and can influence vigilance and attention in potentially threatening environments. In male animals, various types of stress including IMO, were shown to trigger marked elevations in TH and DBH gene expression in the LC [(Smith et al 1991; Melia et al 1992; Rusnak et al 1998; Wang et al 1998; Serova et al 1999; Osterhout et al 2005) reviewed in (Sabban and Kvetnansky 2001; Kvetnansky et al 2009)]. In contrast, in the OVX female rats with low estradiol levels, IMO stress is not effective to trigger an elevation in the LC of TH mRNA and only DBH mRNA levels are increased.…”

Section: Discussionmentioning

confidence: 99%

Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists

Serova¹,

Harris²,

Maharjan³

et al. 2010

Journal of Endocrinology

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Previously, pretreatment with estradiol benzoate (EB) was found to modulate the response of hypothalamic-pituitary-adrenal (HPA) axis and gene expression in several catecholaminergic neuronal locations in ovariectomized (OVX) rats exposed to single immobilization stress (IMO). Here, we investigated the role of estrogen receptor (ER) subtypes, using selective agonists for ERa (propyl pyrazole triol, PPT) or ERb (WAY-200070) in two major central noradrenergic systems and the HPA axis after exposure to single and repeated IMO. OVX female rats received 21 daily injections of either EB (25 mg/kg), PPT (10 mg/kg), WAY-200070 (10 mg/kg), or vehicle. Injections of EB and PPT, but not WAY-200070, elicited reduced body weight and increased uterine weight, showing their selectivity. Both EB and PPT increased corticosterone levels about two-to threefold, but prevented any further rise with either single or repeated IMO, indicating an ERa (ESR1)-, but not ERb (ESR2)-, mediated mechanism. In the locus coeruleus (LC), the rise in dopamine-b-hydroxylase (Dbh) mRNA with both stress paradigms was abrogated in EB-or PPT-injected animals. However, WAY-200070 blocked the response of DBH mRNA to single IMO but not to repeated IMO. In the nucleus of the solitary tract (NTS), the rise in tyrosine hydroxylase and DBH mRNAs with both IMOs was absent, or greatly attenuated, in EB-or PPT-treated rats. In most cases, WAY-200070 inhibited the response to single IMO but not to repeated IMO. The results demonstrate that pretreatment with estradiol, or ER-selective agonists, modulates the stress-triggered induction of gene expression of norepinephrine biosynthetic enzymes in LC and NTS, with ER selectivity depending on duration of the stress.

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Section: Discussionmentioning

confidence: 99%

Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists

Serova¹,

Harris²,

Maharjan³

et al. 2010

Journal of Endocrinology

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“…Exposure to many types of physiological, social or pharmacological stressors, such as cold, restraint, footshock, isolation, forced walking and chronic social stress (but not insulininduced hypoglycemia or chronic mild intermittent stress) elevate TH mRNA in the LC (Angulo et al 1991;Smith et al 1991;Mamalaki et al 1992;Melia et al 1992;Watanabe et al 1995;Rusnak et al 1998;Wang et al 1998).…”

Section: Immobilization Stressmentioning

confidence: 99%

Influence of prior experience with homotypic or heterotypic stressor on stress reactivity in catecholaminergic systems

Sabban

Serova

2007

Stress

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Here we review how prior experience with stress alters the response to a subsequent homotypic or heterotypic stressor, focusing on the catecholaminergic systems in the adrenal medulla and the locus coeruleus (LC). The changes in response to homotypic stress differ depending on the stressor applied. With immobilization stress (IMO), transcriptional responses in the adrenal medulla to a single exposure are pronounced and several of the transcription factors and signaling kinases induced or activated are reviewed and compared to the longer term alterations with repeated stress, consistent with persistent activation of gene expression of catecholamine (CA) biosynthetic enzymes. In the LC, transcriptional and post-transcriptional activation of gene expression are shown to be important. Repeated IMO stress triggers further activation of a number of signalling pathways. Neither adrenal medulla nor LC display habituation to long term repeated stress. In contrast, gene expression for CA biosynthetic enzymes habituates to prolonged cold stress in the adrenal medulla and LC, but displays an exaggerated response with exposure to a novel or heterotypic stressor such as IMO. Some of the transcriptional pathways displaying sensitization are described.

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“…Abnormalities that have been observed in the LC from human depressives (Klimek et al, 1997;Ordway et al, 1994aOrdway et al, , 1994bOrdway et al, , 2003Zhu et al, 1999) can be reproduced, in part, by chronic stress or pharmacological depletion of norepinephrine in rats (Cubells et al, 1995;Lee et al, 1983;Melia et al, 1992;Torda et al, 1985;U'Prichard et al, 1979;Wang et al, 1998;Zafar et al, 1997). Given that stress activates the LC in laboratory animals (Pavcovich et al, 1990), that chronic stress depletes norepinephrine in the LC (Weiss and Simson, 1986), and that stress is a common precipitator of depression in humans, it seems possible that depression may be associated with elevated excitatory input to the LC.…”

Section: Role Of Glutamatergic Signaling In Depressionmentioning

confidence: 99%

“…For example, elevated levels of tyrosine hydroxylase (TH) (Ordway et al, 1994a;Zhu et al, 1999), increased agonist binding to a 2 -adrenergic receptors (Ordway et al, 1994b(Ordway et al, , 2003, and reduced levels of norepinephrine transporters (Klimek et al, 1997) were previously reported in the LC from major depression and in suicide victims. Interestingly, depletion of norepinephrine or repeated stress in rats can increase TH expression, increase binding to a 2 -adrenergic receptors, and/or decrease binding to the norepinephrine transporter (Cubells et al, 1995;Lee et al, 1983;Melia et al, 1992;Torda et al, 1985;U'Prichard et al, 1979;Wang et al, 1998;Zafar et al, 1997). Together, these findings are highly suggestive of dysfunctional noradrenergic neurotransmission in depression, possibly through stress-induced activation and ultimate depletion of norepinephrine.…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

Karolewicz

Stockmeier

Ordway

2005

Neuropsychopharmacol

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Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NR1 and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher ( þ 61%, p ¼ 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum ( þ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.

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Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model rats and rats exposed to short- and long-term forced walking stress

Cited by 31 publications

References 20 publications

Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists

Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists

Influence of prior experience with homotypic or heterotypic stressor on stress reactivity in catecholaminergic systems

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

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