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Reporter mouse strain provides a novel look at angiotensin type-2 receptor distribution in the central nervous system.
- Source :
-
Brain structure & function [Brain Struct Funct] 2016 Mar; Vol. 221 (2), pp. 891-912. Date of Electronic Publication: 2014 Nov 27. - Publication Year :
- 2016
-
Abstract
- Angiotensin-II acts at its type-1 receptor (AT1R) in the brain to regulate body fluid homeostasis, sympathetic outflow and blood pressure. However, the role of the angiotensin type-2 receptor (AT2R) in the neural control of these processes has received far less attention, largely because of limited ability to effectively localize these receptors at a cellular level in the brain. The present studies combine the use of a bacterial artificial chromosome transgenic AT2R-enhanced green fluorescent protein (eGFP) reporter mouse with recent advances in in situ hybridization (ISH) to circumvent this obstacle. Dual immunohistochemistry (IHC)/ISH studies conducted in AT2R-eGFP reporter mice found that eGFP and AT2R mRNA were highly co-localized within the brain. Qualitative analysis of eGFP immunoreactivity in the brain then revealed localization to neurons within nuclei that regulate blood pressure, metabolism, and fluid balance (e.g., NTS and median preoptic nucleus [MnPO]), as well as limbic and cortical areas known to impact stress responding and mood. Subsequently, dual IHC/ISH studies uncovered the phenotype of specific populations of AT2R-eGFP cells. For example, within the NTS, AT2R-eGFP neurons primarily express glutamic acid decarboxylase-1 (80.3 ± 2.8 %), while a smaller subset express vesicular glutamate transporter-2 (18.2 ± 2.9 %) or AT1R (8.7 ± 1.0 %). No co-localization was observed with tyrosine hydroxylase in the NTS. Although AT2R-eGFP neurons were not observed within the paraventricular nucleus (PVN) of the hypothalamus, eGFP immunoreactivity is localized to efferents terminating in the PVN and within GABAergic neurons surrounding this nucleus. These studies demonstrate that central AT2R are positioned to regulate blood pressure, metabolism, and stress responses.
- Subjects :
- Animals
Brain metabolism
GABAergic Neurons metabolism
Hypothalamus metabolism
Immunohistochemistry
Male
Mice
Mice, Transgenic
Models, Animal
Paraventricular Hypothalamic Nucleus metabolism
Preoptic Area metabolism
RNA, Messenger metabolism
Tyrosine 3-Monooxygenase metabolism
Vesicular Glutamate Transport Protein 2 metabolism
Central Nervous System metabolism
Receptor, Angiotensin, Type 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1863-2661
- Volume :
- 221
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Brain structure & function
- Publication Type :
- Academic Journal
- Accession number :
- 25427952
- Full Text :
- https://doi.org/10.1007/s00429-014-0943-1