Targeting brain stem centers of cardiovascular control using adenoviral vectors: impact of promoters on transgene expression

Lonergan, Tina; Teschemacher, Anja G.; Hwang, Deuk-Soo; Ks, Kim; Pickering, Anthony E.; Kasparov, Sergey

doi:10.1152/physiolgenomics.00120.2004

Cited by 55 publications

(60 citation statements)

References 45 publications

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“…This made possible recordings of quantal release events from genetically targeted NAergic green fluorescent protein (EGFP)-expressing neurons in an organotypic brain-slice culture (Teschemacher et al 2005a,b). The PRSx8 promoter that was used to drive EGFP expression, with few exceptions, operates specifically in NAergic and adrenergic neurons (Hwang et al 2001;Lonergan et al 2005). EGFP expression in these slice cultures was consistent with the locations corresponding to A2 neurons in the nucleus of the solitary tract and the ventral A1 group (Paxinos & Watson 1986).…”

Section: New Insights Into the Quantal Characteristics Of Noradrenalisupporting

confidence: 67%

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The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

Kasparov

Teschemacher²

2009

Phil. Trans. R. Soc. B

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In contrast to some other neuronal populations, for example hippocampal or cortical pyramidal neurons, mechanisms of synaptic integration and transmitter release in central neurons that contain noradrenaline (NA) and serotonin (5HT) are not well understood. These cells, crucial for a wide range of autonomic and behavioural processes, have long un-myelinated axons with hundreds of varicosities where transmitters are synthesized and released. Both seem to signal mostly in 'volume transmission' mode. Very little is known about the rules that apply to this type of transmission in the brain and the factors that regulate the release of NA and 5HT. We discuss some of our published studies and more recent experiments in which viral vectors were used to investigate the physiology of these neuronal populations. We also focus on currently unresolved issues concerning the mechanism of volume transmission by NA and 5HT in the brain. We suggest that clarifying the role of astroglia in this process could be essential for our understanding of central noradrenergic and 5HT signalling.

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Section: New Insights Into the Quantal Characteristics Of Noradrenalisupporting

confidence: 67%

“…Direct characterization of NA release in mammalian brain was made possible using a viral vector with PRSx8 promoter that labels mainly CAergic cells (Lonergan et al 2005). We therefore decided to develop a viral system for targeting 5HTergic neurons.…”

Section: Viral Vectors For Selective Targeting Of Serotonergic (5htermentioning

confidence: 99%

The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

Kasparov

Teschemacher²

2009

Phil. Trans. R. Soc. B

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“…We have recently described that adenoviruses with the human CMV promoter drive extremely low levels of gene expression in most NTS neurons. 31 On the other hand, these vectors clearly transduce local vasculature. 11 Based on evidence that JAM-1 can cause leukocyte and platelet adhesion in the peripheral circulation, 24 -26 it was necessary to assess whether this could occur within the brain after inducing JAM-1 overexpression.…”

Section: Possible Mechanisms By Which Jam-1 In Nts Elevates Arterial mentioning

confidence: 99%

Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats

et al. 2007

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Abstract-Junctional adhesion molecule-1 (JAM-1) forms part of the tight junction between adjacent endothelial cells.Using microarray technology, we showed previously that JAM-1 was differentially expressed in the brain stem of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto (WKY) rats. In this study, we quantified the expression of JAM-1 in the brain stem of spontaneously hypertensive rats and WKY rats and established whether any differential expression was confined to this region of the brain or was ubiquitous throughout the central nervous system and, indeed, the whole body. Because the nucleus tractus solitarii plays a pivotal role in arterial pressure regulation, we assessed whether JAM-1 in this region affects the chronic regulation of arterial pressure. Real time RT-PCR revealed that JAM-1 mRNA was upregulated in multiple regions of the brain and all of the peripheral vascular beds studied. In the nucleus tractus solitarii, the level of JAM-1 mRNA was significantly higher in both young (3-week-old, prehypertensive) and adult male spontaneously hypertensive rats (15 to 18 weeks old) than that of age-matched WKY rats (fold differences; prehypertensives: 1.01Ϯ0.06 versus 1.59Ϯ0.13; nϭ10; PϽ0.01; adult: 1.08Ϯ0.14 versus 2.86Ϯ0.57; nϭ10; PϽ0.01). After adenoviral-mediated expression of JAM-1 in the nucleus tractus solitarii of adult WKY rats (15 weeks old; nϭ6), systolic pressure was increased from 120Ϯ4 to 132Ϯ4 mm Hg (PϽ0.01). Our data suggest that JAM-1 expression in the spontaneously hypertensive rat is upregulated throughout the body compared with the WKY rat and that this is not secondary to the hypertension. When JAM-1 is expressed in the nucleus tractus solitarii, it raises arterial pressure, suggesting a novel prohypertensive role for this protein within the brain stem. Key Words: hypertension Ⅲ brain stem Ⅲ inflammation Ⅲ baroreflex control Ⅲ adhesion molecules E ssential hypertension is a complex polygenic trait with underlying genetic components, many of which remain unknown. Unmasking these genes may provide novel information about blood regulation and could be potential future targets for therapeutic intervention. This is pertinent, because Ϸ50% of patients with hypertension on antihypertensive medication continue to have elevated levels of blood pressure (www.heartstats.org). 1 Despite accumulating evidence that gene expression profiles are altered in essential hypertension, 2,3 prohypertensive genes remain unclear. One confounding factor is that hypertension itself induces changes in gene expression as a secondary effect.We are exploring the role of the autonomic nervous system in the etiology of hypertension. It is documented that human essential hypertension is associated with a high level of sympathetic nerve activity in humans. 4 -6 Grassi 6 postulated that neurogenic hypertension is maintained by sympathetic overactivity and that this may even be causative. Consistent with that viewpoint, Smith et al 5 have shown sympathetic overactivity in white coat hypertensive s...

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“…Rats were left to recover for seven days. This time is necessary for maximal expression of transfected gene (Lonergan T et al, 2005). All procedures were carried out in an RNase-free environment and all solutions made up using RNase-free water/reagents.…”

Section: Transfectionmentioning

confidence: 99%

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

Lozić

Tasić

Martin

et al. 2016

Pharmacological Research

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The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress.Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress.However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology. KeywordsVasopressin, V1a receptor, paraventricular nucleus, adenoviral vector, baroreflex, blood pressure variability, heart rate variability Abbreviations BRS, baroreflex sensitivity; VLF, very low frequency short-term variability; LF, low frequency short-term variability; HF, high frequency short-term variability; VP, vasopressin;OT, oxytocin; OTR, oxytocin receptor; V1aR, vasopressin V1a receptor; V1bR, vasopressin V1b receptor; V2R, vasopressin V2 receptor; V1aRX, vasopressin V1a receptor antagonist, PVN, paraventricular nucleus; NTS, nucleus of the solitary tract; RVLM; rostroventrolateral medulla; IML, intermediolateral column of the spinal cord.

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Targeting brain stem centers of cardiovascular control using adenoviral vectors: impact of promoters on transgene expression

Cited by 55 publications

References 45 publications

The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

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