Human sympathetic nerve biology : parallel influences of stress and epigenetics in essential hypertension and panic disorder

Esler, Murray, Eikelis, Nina, Schlaich, Markus, Lambert, Gavin, Alvarenga, Marlies, Kaye, David, El-Osta, Assam, Guo, Ling, Barton, David, Pier, Ciaran, Brenchley, Celia, Dawood, Tye, Jennings, Garry and Lambert, Elisabeth 2008, Human sympathetic nerve biology : parallel influences of stress and epigenetics in essential hypertension and panic disorder, Annals of the New York Academy of Sciences, vol. 1148, pp. 338-348, doi: 10.1196/annals.1410.064.

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Title Human sympathetic nerve biology : parallel influences of stress and epigenetics in essential hypertension and panic disorder
Author(s) Esler, Murray
Eikelis, Nina
Schlaich, Markus
Lambert, Gavin
Alvarenga, Marlies
Kaye, David
El-Osta, Assam
Guo, Ling
Barton, David
Pier, Ciaran
Brenchley, Celia
Dawood, Tye
Jennings, Garry
Lambert, Elisabeth
Journal name Annals of the New York Academy of Sciences
Volume number 1148
Start page 338
End page 348
Publisher Wiley-Blackwell
Place of publication Oxford, England
Publication date 2008-12
ISSN 0077-8923
Keyword(s) norepinephrine
nerve growth factor
norepinephrine neuronal reuptake
stress biomarkers
Summary Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress—a disputed proposition—we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation-related inhibitory transcription factor MeCP2.
Language eng
DOI 10.1196/annals.1410.064
Field of Research 170101 Biological Psychology (Neuropsychology)
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
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Document type: Journal Article
Collections: Faculty of Health
School of Psychology
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