Comparison of the efficacy of four viral vectors for transducing hypothalamic magnocellular neurosecretory neurons in the rat supraoptic nucleus

Doherty, Faye; Schaack, Jerome; Sladek, Celia D.

doi:10.1016/j.jneumeth.2011.02.026

Cited by 18 publications

(13 citation statements)

References 61 publications

(86 reference statements)

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“…In addition, viral vectors have been successfully used to study gene promoter domains that are involved in cell-specific gene expression in vivo [27], [38], [41], [42], [43], [44] and AAV vectors have been shown to be more efficient than lentiviral vectors in transducing neurons in the forebrain [38], [40]. In previous studies it was shown that AAV vectors that contained promoter deletion constructs of the Oxt gene promoter fused to EGFP reporters effectively transduced MCNs in the rat SON in vivo [27], [30].…”

Section: Discussionmentioning

confidence: 99%

Cell-Type Specific Expression of the Vasopressin Gene Analyzed by AAV Mediated Gene Delivery of Promoter Deletion Constructs into the Rat SON In Vivo

Ponzio¹,

Fields²,

Rashid³

et al. 2012

PLoS ONE

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The magnocellular neurons (MCNs) in the supraoptic nucleus (SON) of the hypothalamus selectively express either oxytocin (Oxt) or vasopressin (Avp) neuropeptide genes. In this paper we examine the cis-regulatory domains in the Avp gene promoter that are responsible for its cell-type specific expression. AAV vectors that contain various Avp gene promoter deletion constructs using EGFP as the reporter were stereotaxically injected into the rat SON. Two weeks following the injection immunohistochemical assays of EGFP expression from these constructs were done to determine whether the expressed EGFP reporter co-localizes with either the Oxt- or Avp-immunoreactivity in the MCNs. The results identify three major enhancer domains located at −2.0 to −1.5 kbp, −1.5 to −950 bp, and −950 to −543 bp in the Avp gene promoter that regulate the expression in Avp MCNs. The results also show that cell–type specific expression in Avp MCNs is maintained in constructs containing at least 288 bp of the promoter region upstream of the transcription start site, but this specificity is lost at 116 bp and below. Based on these data, we hypothesize that the −288 bp to −116 bp domain contains an Avp MCN specific activator and a possible repressor that inhibits expression in Oxt-MCNs, thereby leading to the cell-type specific expression of the Avp gene only in the Avp-MCNs.

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Section: Discussionmentioning

confidence: 99%

Cell-Type Specific Expression of the Vasopressin Gene Analyzed by AAV Mediated Gene Delivery of Promoter Deletion Constructs into the Rat SON In Vivo

Ponzio¹,

Fields²,

Rashid³

et al. 2012

PLoS ONE

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“…Nevertheless, CED has been used to successfully enhance cell infection and viral distribution in the brain in both animal models and clinical trials, albeit with limited treatment efficacy (Rampling et al, 2000;Hadjipanayis et al, 2008;Ryan et al, 2010;Carty et al, 2011;Doherty et al, 2011). It has been theorized that the limited success of these trials is a result of the lack of optimization of this technique for the delivery of viral vectors to the brain (White et al, 2011a,b).…”

mentioning

confidence: 99%

Strategies to Enhance Viral Penetration of Solid Tumors

2011

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The efficient delivery of viral vectors to tumors is an active area of investigation. A number of barriers exist that must be overcome to achieve good penetration of vectors into tumors and distribution of their effects throughout the tumor mass. Replicating oncolytic viruses have the advantage of being able to amplify the initial dose, but progeny virus are prevented from spreading because of a dense mass of tightly packed cells with a dense extracellular matrix, admixed normal stromal cells, and high interstitial pressure. Although intratumoral injection may ensure initial delivery the distribution achieved by intravenous administration may be superior and come with beneficial bystander damage to the tumor vasculature. Strategies to enhance intravenous delivery and subsequent spread of these vectors within tumors are being developed by a number of groups. Achieving the goal of efficient penetration and spread of viruses within solid tumors is a necessary prerequisite to significant improvements in virus-vectored therapy of solid tumors.

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“…Thus, there is a possibility that ectopic V1aR located on astrocytes could be involved (Doherty et al, 2011;Tasker et al, 2012) in the modulation of neuronal activity in the PVN.…”

Section: Discussionmentioning

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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Comparison of the efficacy of four viral vectors for transducing hypothalamic magnocellular neurosecretory neurons in the rat supraoptic nucleus

Cited by 18 publications

References 61 publications

Cell-Type Specific Expression of the Vasopressin Gene Analyzed by AAV Mediated Gene Delivery of Promoter Deletion Constructs into the Rat SON In Vivo

Cell-Type Specific Expression of the Vasopressin Gene Analyzed by AAV Mediated Gene Delivery of Promoter Deletion Constructs into the Rat SON In Vivo

Strategies to Enhance Viral Penetration of Solid Tumors

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

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