IngentaConnect Circumventricular Organs: Gateways to the Brain Approaches For Ge...

Authors: Vasquez, Elisardo C¹; Meyrelles, Silvana S¹; Chapleau, Mark W; Johnson, Alan Kim

Source: Clinical and Experimental Pharmacology and Physiology, Volume 28, Number 7, July 2001 , pp. 602-609(8)

Abstract:

SUMMARY

1. The subfornical organ (SFO), the magnocellular neurons in supraoptic (SON) and paraventricular (PVN) nuclei and the neurohypophysis (NH) constitute an important neuroendocrine axis for the maintenance of cardiovascular and body fluid homeostasis in mammals. The SFO lacks a blood-brain barrier and is an important target for the effects of circulating angiotensin II on thirst. The SON and PVN, which receive projections from the SFO, synthesize the peptide vasopressin, which is stored in the NH nerve terminals and is released into the circulation under conditions of hypovolaemia and hyperosmolality.

2. Although neuropharmacological methods are still of fundamental importance for the understanding of the central nervous system (CNS), the techniques of gene transfer to the CNS that have been developed recently provide a new means to study and influence neural function. A key vector for delivering reporter or functional genes to the brain has been replication-deficient adenovirus, because it is safer, can be generated in high titres, can transfect non-dividing cells and can be retrogradely transported from nerve terminals to somata.

3. In the present review, we describe new approaches that have been developed to transfer genes to the SFO, SON, PVN and NH cells both in vitro and in vivo. We have defined the adenoviral concentrations required to optimize gene expression without causing cytotoxicity and an inflammatory response in the target cells. Gene transfer is an important tool to reveal mechanisms of SFO and SON control of cardiovascular homeostasis and may provide a therapeutic approach for prevention and/or treatment of pathophysiologies, such as arterial hypertension and genetic diabetes insipidus.

Keywords: adenovirus; gene delivery; magnocellular neurons; subfornical organ

Document Type: Research article

DOI: 10.1046/j.1440-1681.2001.03492.x

Affiliations: 1: Department of Physiological Sciences, Biomedical Center (UFES) and Health Sciences College (Emescam), Vitoria, Brazil and Departments of

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Circumventricular Organs: Gateways to the Brain Approaches For Gene Delivery To The Subfornical Organ And Magnocellular Neurons