Stress Neurobiology
Research
Research projects
The work in our laboratory focuses on understanding the link between psychological stress, the central nervous system and cardiovascular health. In particular, we investigate subcellular, cellular and neuronal circuit mechanisms that translate negative emotional reactions into sympathetic and cardiovascular activation, and ultimately cardiovascular disease risk.
Molecular, cellular and neuroanatomical substrates of sympathetic response to acute stress
This project aims to identify neural mechanisms that underlie the sympathoexcitatory effect of acute psychological stress. Particular focus is placed on the role of redox-sensitive signal transduction in presympathetic areas of the hypothalamus and brainstem. Apart from neurons, the project investigates the potential role of glial and perivascular cells in redox-sensitive modulation of central autonomic function during acute stress. The project utilizes pharmacological, molecular (viral gene transfer) and confocal imaging approaches in both in vitro (living brain slices) and in vivo preparations. These studies are conducted in collaboration with the laboratories of Prof. J. Paton and Dr. S. Kasparov, the Univ. of Bristol, UK.
Long-term neural regulation of cardiovascular reactivity to stress
The magnitude of cardiovascular reactivity varies largely between individuals and chronically increased reactivity is considered to be a risk factor for heart and vascular disease. The project aims to identify long-term molecular mechanisms that set the level of cardiovascular reactivity to psychological stress. Special focus is given to the role of redox-sensitive protein kinases and transcription factors implicated in long-term control of synaptic plasticity. These studies combine activation/inactivation of selected signalling proteins in presympathetic brain areas in vivo and experimentalmodels of recurrent stress including fear conditioning paradigm.
Brain redox state, stress reactivity and cardiovascular disease risk
Based on the findings of the above studies, this project aims to clarify the link between the brain redox state, stress reactivity and susceptibility to stress-induced ventricular arrhythmias. These studiesutilize radiotelemetry monitoring of blood pressure and ECG in rodent strains characterized by different levels of stress reactivity, experimentalmodels of psychological stress and functional neuroimaging techniques.
Key References
- Mayorov DN, Head GA & De Matteo R. Tempol attenuates excitatory actions of angiotensin II in the rostral ventrolateral medulla during emotional stress. Hypertension 2004; 44:101-106.
- Mayorov DN. Selective sensitization by nitric oxide of sympathetic baroreflex in rostral ventrolateral medulla of conscious rabbits. Hypertension 2005; 45:901-906.
- De Matteo R, Head GA & Mayorov DN. Angiotensin II in dorsomedial hypothalamus modulates cardiovascular arousal caused by stress but not feeding in rabbits. Am J Physiol 2006; 290:R257-R264.
- Jackson K, Head GA, Morris BJ, Chin-Dusting J, Jones E, La Greca L & Mayorov DN. Reduced cardiovascular reactivity to stress but not feeding in renin enhancer knockout mice. Am J Hypertens, 2007; 20: 893-899.
- Mayorov DN. Brain angiotensin and cardiovascular reactivity to negative and positive emotional stress. Curr Hypertens Reviews, 2007; 3: 105-117.
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