Regulation of Gene Expression of Catecholamine Biosynthetic Enzymes in Dopamine‐β‐Hydroxylase‐ and CRH‐Knockout Mice Exposed to Stress (original) (raw)
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Annals of the New York Academy of Sciences, 2008
Norepinephrine-deficient mice harbor a disruption of the gene for dopamine-β-hydroxylase (DBH-KO). Corticotropin-releasing hormone knockout mice (CRH-KO) have markedly reduced HPA activity. The aim of the present work was to study how deficiency of DBH and CRH would affect tyrosine hydroxylase (TH), DBH, and phenylethanolamine N-methyltransferase (PNMT) gene expression and protein levels in the adrenal medulla (AM) and stellate ganglia (SG) of control and stressed mice. Both in AM and SG, single immobilization significantly increased TH and DBH mRNA and protein levels both in wild-type (WT) and CRH-KO mice. On the other hand, the stress-triggered increase in the PNMT mRNA and protein levels seen in WT mice was absent in CRH KO mice. DBH-KO mice are more sensitive to stress but survive a single 2 h restraint stress in a tube (RES). The increase in TH mRNA levels induced by RES in WT was not observed in DBH-KO mice. PNMT mRNA and especially PNMT protein levels were significantly elevated in AM of DBH-KO mice. In SG of DBH-KO mice TH mRNA levels were not affected; however, PNMT gene expression was highly elevated. Thus, disruption of the DBH gene surprisingly blocks the stress-induced elevation of TH mRNA levels in AM but increases PNMT gene expression both in AM and SG. Our data indicate that adrenergic signaling is required for stressinduced increase in TH mRNA and that this signaling restrains stress-induced increase in PNMT mRNA. They also confirm that the HPA system plays a crucial role in the stress-induced regulation of PNMT gene expression.
Gene expression of catecholamine synthesizing enzymes in stellate ganglia of stressed rats
Acta veterinaria, 2010
Enhanced activation of sympathetic neurons during stress results in an increased cardiovascular function. Social isolation is a psychological stress which has deleterious effects on health and represents the most relevant cause of diseases in mammalian species. In this study we investigated the changes in catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine b-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) gene expression and protein levels in the stellate ganglia of naive controls and chronically socially isolated (12 weeks) adult rats and the response of these animals to additional immobilization stress (2 h) by applying TaqMan RT-PCR assay and Western blot analysis. Psychosocial stress produced a significant increase of both TH mRNA (p<0.05) and DBH mRNA (p<0.05) levels in stellate ganglia. The exposure of control rats to acute immobilization significantly increased TH mRNA (p<0.001) and DBH mRNA (p<0.01) levels, while additional immobilization of chronic psychosocially stressed rats expressed no effect on gene expression of these enzymes. Protein levels of TH, and DBH remained unchanged in control and chronic social isolation rats and also after short-term immobilization. The results presented here suggest that psychosocial stress-induced an increase in gene expression of catecholamine biosynthetic enzymes in stellate ganglia and thus may be connected to the increased risk of cardiovascular disease.
Journal of Neurochemistry
Adrenal catecholamines are known to mediate many of the physiological consequences of the "fight or flight" response to stress. However, the mechanisms by which the long-term responses to repeated stress are mediated are less well understood and possibly involve alterations in gene expression. In this study the effects of a single and repeated immobilization stress on mRNA levels of the adrenal catecholamine biosynthetic enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase, were examined. A repeated 2-hr daily immobilization for 7 consecutive days markedly elevated both tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels (about six- and fourfold, respectively). In contrast, tyrosine hydroxylase but not dopamine beta-hydroxylase mRNA levels were elevated immediately following a single immobilization. The elevation in tyrosine hydroxylase mRNA with a single immobilization was as high as with seven daily repeated immobilizations. This elevation was not susta...
Autonomic Neuroscience, 2009
In this study we investigated the changes in norepinephrine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) gene expression in the stellate ganglia of naive controls and long-term socially isolated (12 weeks) adult rats and the response of these animals to additional immobilization stress. Psychosocial stress produced a significant increase of both TH mRNA and DBH mRNA levels in stellate ganglia. Additional immobilization of long-term psychosocially stressed rats expressed no effect on gene expression of these enzymes. The results presented here suggest that psychosocial stress-induced increase in gene expression of norepinephrine biosynthetic enzymes in stellate ganglia may be connected to the increased risk of cardiovascular disease.
Molecular Brain Research, 2000
Norepinephrine NE is thought to play a role in the stress response, and may be involved in stress-related psychopathological conditions such as depression or anxiety. Heterogeneity in individual responses to the same stressor suggest that a genetic susceptibility to the effects of stress may contribute to such pathology. To address possible mechanisms underlying this genetic aspect of the stress response, we examined acute stress-induced changes in mRNA expression for several components of the NE system in the locus Ž . Ž . Ž . coeruleus LC and adrenal medullae of stress-susceptible Wistar-Kyoto WKY rats and their parent Wistar W strain. Expression of Ž . Ž . tyrosine hydroxylase TH , NE transporter NET and a receptor mRNA were measured in the LC by in situ hybridization 30 min and 2A 2 h after the onset of 30 min restraint stress. Adrenal TH mRNA was measured by slot blots. No basal differences were observed for any Ž . measure, but in the LC, expression of TH mRNA increased by 40% in W rats at 30 min n s 8, p -0.05 and returned toward baseline by 2 h, while WKY rats showed only a non-significant 29% increase at 2 h. In contrast, adrenal TH mRNA expression increased in WKY Ž . rats at 2 h n s 3, p -0.05 , with no significant change in W rats. NET and a mRNA were unaltered by restraint stress in both strains.
Physiological Research
Stress exposure activates the sympathoneural system, resulting in catecholamine release. Chronic stress is associated with development of numerous disorders, including cardiovascular diseases. Here we investigated the expression of mRNAs for catecholamine biosynthetic enzymes tyrosine-hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyl-transferase, and for ß1- and ß2-adrenoceptors in the right and left ventricles of rats exposed to chronic unpredictable mild stress. The tyrosine-hydroxylase and dopamine-ß-hydroxylase mRNA levels were not affected by stress, whereas the phenylethanolamine N-methyltransferase mRNA levels significantly increased in both right and left ventricles. No changes in ß1–adrenoceptor mRNA levels in either right or left ventricles were observed. At the same time, stress produced a significant increase of β2-adrenoceptor mRNA levels in left ventricles. These results suggest that elevated expression of phenylethanolamine N-methyltransferase in bot...
Psychoneuroendocrinology, 2014
The aim of the present work was to study the influence of variable stress on the expression of 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress al...
Regulation of atrial catecholamine enzymes and adrenoceptor gene expression after chronic stress
Acta Physiologica Hungarica, 2011
Chronic stress is a risk factor for the development of numerous psychopathological conditions in humans including depression. Changes in gene expression of tyrosine-hydroxylase (TH), dopamine-β-hydroxylase (DBH) phenylethanolamine N-methyltransferase (PNMT), ß 1-, ß 2-and ß 3-adrenoceptors in right and left rat atria upon chronic unpredictable mild stress (CMS) were investigated. CMS decreased TH and DBH gene expression levels both in right and left atria and increased PNMT mRNA in left atria. No changes in mRNA levels of ß 1-and ß 2adrenoceptors were recorded, whereas ß 3-adrenoreceptor mRNA level was significantly elevated in right atria of CMS rats. At the same time, CMS produced a significant increase of β 1-and β 2-adrenoreceptor mRNA levels in left atria, but did not affect β 3-adrenoceptor mRNA level. The results presented here suggest that stress-induced depression expressed differential effects on catecholamine biosynthetic enzymes and ß-adrenoceptors at molecular level in right and left atria of adult rat males. Elevated gene expression of PNMT in left atria of rats exposed to CMS can lead to altered physiological esponse and may play a role in the pathophysiology of cardiovascular function.
Neuroscience, 2010
Stress responses are elicited by a variety of stimuli and are aimed at counteracting direct or perceived threats to the well-being of an organism. In the mammalian central and peripheral nervous systems, specific cell groups constitute signaling circuits that indicate the presence of a stressor and elaborate an adequate response. Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in central and peripheral parts of these circuits and has recently been identified as a candidate for regulation of the stress axis. In the present experiments, we tested the involvement of PACAP in the response to a psychological stressor in vivo. We used a restraint paradigm and compared PACAP-deficient mice (PACAP؊/؊) to wild-type controls (PACAP؉/؉). Acute secretion of corticosterone elicited by 1 h of restraint was found to be identical between genotypes, whereas sustained secretion provoked by 6 h of unrelieved restraint was 48% lower in PACAP؊/؊mice. Within the latter time frame, expression of messenger RNA (mRNA) encoding corticotropin-releasing hormone (CRH) was increased in the hypothalamus of wild type, but not PACAP-deficient mice. Expression of the activity-regulated transcription factors Egr1 (early growth response 1) and Fos (FBJ osteosarcoma oncogene) in the hypothalamus was rapidly and transiently induced by restraint in a PACAP-dependent fashion, a pattern that was also found in the adrenal glands. Here, abundance of transcripts encoding enzymes required for adrenomedullary catecholamine biosynthesis, namely TH (tyrosine hydroxylase) and PNMT (phenylethanolamine N-methyltransferase), was higher in PACAP؉/؉ mice after 6 h of unrelieved restraint. Our results suggest that sustained corticosterone secretion, synthesis of the hypophysiotropic hormone CRH in the hypothalamus, and synthesis of the enzymes producing the hormone adrenaline in the adrenal medulla, are controlled by PACAP signaling in the mouse. These findings identify PACAP as a major contributor to the stimulus-secretion-synthesis coupling that supports stress responses in vivo. Published by Elsevier Ltd on behalf of IBRO.