Adenovirus-Mediated Gene Delivery to Hypothalamic Magnocellular Neurons in Mice

Vasquez, Elisardo C.; Beltz, Terry G.; Meyrelles, Silvana S.; Johnson, Alan Kim

doi:10.1161/01.hyp.34.4.756

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…We have observed EGFP-containing axons following this route. These findings complement the report that injection of adenovirus encoding EGFP into the posterior pituitary can result in EGFP expression in the magnocellular neurones of the PVN and SON via retrograde transport [16, 17]. …”

Section: Discussionsupporting

confidence: 87%

Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus

Ward

Gardiner²,

Kong³

et al. 2003

Neuroendocrinology

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We have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. Gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. We have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. Cell bodies containing enhanced green fluorescent protein were also visualized in the paraventricular nucleus contralateral to the side of injection. These findings suggest that gene transfer by recombinant adeno-associated virus could be used as a tool to investigate hypothalamic-pituitary interactions and, elsewhere in the central nervous system, to trace axonal pathways.

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Section: Discussionsupporting

confidence: 87%

Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus

Ward

Gardiner²,

Kong³

et al. 2003

Neuroendocrinology

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“…A similar strategy has been used to successfully target genes back to neurons of the PVN and SON via pituitary injections of an Ad vector. 34 We are currently investigating the feasibility of inducing transgene expression in additional functionally unique subgroups of SFO neurons by selectively injecting Ad␤-gal into its other sites of projection, eg, PVN and median preoptic nucleus.…”

Section: Discussionmentioning

confidence: 99%

Selective Gene Transfer to Key Cardiovascular Regions of the Brain: Comparison of Two Viral Vector Systems

et al. 2002

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Abstract-The systemic renin-angiotensin system (RAS) plays a critical role in cardiovascular (CV) homeostasis. All components of the RAS are also known to be produced cell-specifically within specific brain regions, although the role of the brain RAS relative to the systemic RAS has remained a puzzle due to the difficulty of dissecting these two systems. Selectively targeting these regions with genes that modify the RAS could help unravel this puzzle. We compared the ability of adenovirus (Ad) and lentivirus (feline immunodeficiency virus, FIV) vectors to mediate gene delivery in vivo to the supraoptic nucleus (SON) and subfornical organ (SFO), two important CV control regions known to express the various RAS genes. SON or SFO of adult C57BL/6 mice (nϭ37) were stereotaxically injected with replication-deficient recombinant Ad or FIV harboring a ␤-galactosidase (␤-gal) reporter gene. At 1, 3, or 8 weeks post-injection, brain sections were processed for ␤-Gal activity, double immunofluorescence to verify cell-type specificity of viral transduction, or immunohistochemical detection of inflammatory mediators. Our results demonstrate that: (1) murine SFO and SON can be selectively targeted for gene transfer in vivo;(2) FIV mediated neuron-specific gene delivery, whereas Ad transduced both neuronal and glial cell types in SFO and SON; (3) Ad injected into the SON transduced neurons within the SFO through retrograde transport, whereas FIV did not; (4) ␤-gal activity remained stable for 3 weeks but then declined by 8 weeks with Ad, while minimal decline occurred with FIV; (5) Key Words: renin-angiotensin system Ⅲ brain Ⅲ gene regulation T he importance of the classic systemic renin-angiotensin system (RAS) in cardiovascular (CV) and volume homeostasis is well established. However, the CV regulatory role of intrinsic tissue RAS, defined as tissue-based systems with the potential for local angiotensin II (Ang-II) production and action, remain unresolved because of the difficulty in experimentally dissecting tissue and systemic RAS. The brain RAS 1 has remained particularly puzzling, in part because of the direct interfacing of the brain and systemic RAS at circumventricular organs (devoid of a blood-brain-barrier), and an inability to manipulate the brain RAS cell and site selectively.The RAS in the forebrain neural circuitry containing the subfornical organ (SFO)-supraoptic nucleus (SON) axis is one example of a system that is known to be critically involved in blood pressure and body fluid regulation, yet that remains poorly understood because of difficulties in dissecting it. The SFO, a circumventricular organ, is thought to couple blood-borne signals such as Ang-II with brain structures that trigger endocrine and autonomic reflexes designed to restore homeostasis. 2 The hypothalamic nucleus SON, containing magnocellular vasopressinergic neurosecretory cells, receives direct projections from neurons of the SFO. 3,4 Stimulation of the SFO-SON pathway is considered to be important in the control of osmolality and blood ...

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“…However, genetic discoveries and advances in molecular biotechnologies have provided the opportunity to develop many mouse models for human diseases. Although a major disadvantage of this animal is the small size, advances in surgical techniques have overcome this limitation, allowing for studies of cerebral [8, 9], cardiac [10], vascular [11], and renal [12] functions. …”

Section: Induction Of 2k1c Hypertension In the Mousementioning

confidence: 99%

Cardiac-Autonomic Imbalance and Baroreflex Dysfunction in the Renovascular Angiotensin-Dependent Hypertensive Mouse

Campagnaro

Gava

Meyrelles

et al. 2012

International Journal of Hypertension

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Mouse models provide powerful tools for studying the mechanisms underlying the dysfunction of the autonomic reflex control of cardiovascular function and those involved in cardiovascular diseases. The established murine model of two-kidney, one-clip (2K1C) angiotensin II-dependent hypertension represents a useful tool for studying the neural control of cardiovascular function. In this paper, we discuss the main contributions from our laboratory and others regarding cardiac-autonomic imbalance and baroreflex dysfunction. We show recent data from the angiotensin-dependent hypertensive mouse demonstrating DNA damage and oxidative stress using the comet assay and flow cytometry, respectively. Finally, we highlight the relationships between angiotensin and peripheral and central nervous system areas of cardiovascular control and oxidative stress in the 2K1C hypertensive mouse.

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Adenovirus-Mediated Gene Delivery to Hypothalamic Magnocellular Neurons in Mice

Cited by 13 publications

References 23 publications

Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus

Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus

Selective Gene Transfer to Key Cardiovascular Regions of the Brain: Comparison of Two Viral Vector Systems

Cardiac-Autonomic Imbalance and Baroreflex Dysfunction in the Renovascular Angiotensin-Dependent Hypertensive Mouse

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