Adenoviral vectors as functional retrograde neuronal tracers

Ridoux, V.; Robert, Jean Jacques; Zhang, Xia; Perricaudet, Michel; Mallet, Jacques

doi:10.1016/0006-8993(94)91919-4

Cited by 75 publications

(44 citation statements)

References 15 publications

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“…16,17 We examined both X-gal-and immunoflourescenceprocessed sections for ␤-gal-positive cells in sites other than those directly injected with FIV␤-gal or Ad␤-gal. Figure 4 shows a representative example of a double-labeled SFO from an animal that had been injected with Ad␤-gal into SON (bilaterally) 3 weeks earlier.…”

Section: Resultsmentioning

confidence: 99%

“…13 Ad is also known to be taken up by terminals and retrogradely transported to neuronal somata distant to the site of injection. 15,16 In contrast, when the envelop protein of the feline immunodeficiency virus is replaced by the envelop protein from the vesicular stomatitis virus (VSV-G), this VSV-G pseudotyped FIV mediates gene transfer predominantly to neurons rather than to nonneuronal cells, 17 and retrograde transport is limited to local, but not distant, neuronal somata. 17 Additionally, since FIV integrates the transgene into the host genome, transgene expression is highly stable.…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

mentioning

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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“…23 To determine if cell typeoratories have demonstrated the basic feasibility of theraspecific promoters would be useful in facilitating transpeutic gene delivery to peripheral and central neurons gene expression, we investigated the capacity of two with herpes simplex virus-type 1 (HSV-1) and adenovirus putative neuron-specific promoters, the neuron-specific vectors. [4][5][6][7][8][9][10][11][12][13][14] Some of these delivery systems, while enolase (NSE) promoter and the platelet-derived growth promising, present problems that may render them less factor (PDGF) B-chain promoter, to drive the expression of this reporter gene in the adult rat spinal cord. One of the difficulties encountered in using AAV as a vector is…”

Section: Cific Promoters In the Adult Spinal Cord In Anticipation Ofmentioning

confidence: 99%

Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters

et al. 1997

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In this study, we have evaluated the capacity of recombimorphological profiles of transduced cells were consistnant adeno-associated virus (rAAV) vectors, containing cell ently neuronal, and there was no evidence of transgene type-specific promoters, to transduce neurons in vivo in the expression in glial elements. Transduction efficiencies for normal adult rat spinal cord. The neuron-specific enolase the NSE and PDGF rAAVs were estimated at 15 and 45 (NSE) promoter and the platelet-derived growth factor infectious particles per GFP-positive neuron, respectively, (PDGF) B-chain promoter were used to direct expression in the absence of detectable adenovirus. This study of a 'humanized' form of the gene for green fluorescent strongly supports a role for rAAV vectors in CNS gene therprotein (GFP). Neuron-specific rAAVs were injected into apy and lays the groundwork for delivery of more functional the mid-cervical regions of adult rat spinal cords. At genes to spinal cord neurons as a possible way to enhance 10-14 days, expression was detected in all animals and spinal cord repair following injury. persisted for up to 15 weeks. Immunocytochemical and

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“…When Adv/f3-gal vector (2.2 x 108 pfu) was injected intracerebrally, numerous virally infected cells were observed at the injection sites (Fig. 4 G and H) and some weakly stained cells could be detected in other brain areas (data not shown) presumably because of retrograde transport of the viral particles by axons projecting to the injection areas (25,26). In addition, some ,3-gal positive cells were seen in the liver and kidney (data not shown) presumably due to leakage of the viral particles into circulation during the procedure.…”

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confidence: 94%

Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene.

Wang

Krushel²,

Edelman

1996

Proc. Natl. Acad. Sci. U.S.A.

148

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Adenoviral vectors as functional retrograde neuronal tracers

Cited by 75 publications

References 15 publications

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

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

Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters

Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene.

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