Expression of angiotensinogen and receptors for angiotensin and prorenin in the rat and monkey striatal neurons and glial cells.
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system, which function is the regulation of blood pressure. However, it is now known that there exists local RAS in many tissues, including brain. In recent studies, we have demonstrated the presence of a local RAS in the substantia nigra of rodents and primates that modulates dopamine release and dopamine receptor expression. However, overactivation of local RAS exacerbates neuroinflammation, oxidative stress and dopaminergic cell death. In the striatum, it is not clear whether angiotensin receptors are located in dopaminergic terminals, glial cells and/or the projection neurons. The present study shows the location of major components of the RAS in striatal projection neurons of rats and monkeys (both in neurons of the direct and the indirect pathways). Striatal astrocytes and microglial cells also express major RAS components, which increase after induction of neuroinflammation by intrastriatal injection of lipopolysaccharide. Angiotensin receptors were located at the cell surface and also at cytoplasmic and nuclear levels. The results obtained by immunolabeling and confocal microscopy were confirmed with laser microdissection of striatal neurons and glial cells and detection of mRNA expression by PCR. The sequence of the resulting PCR products was verified by DNA sequencing. In addition to the interaction between angiotensin and dopamine receptors in dopaminergic neurons to regulate dopamine release, interaction between angiotensin and dopamine receptors in projection striatal neurons may further modulate the effects of dopamine on the direct and indirect pathways by fine-tuning striatal dopaminergic neurotransmission.
Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Pablo
P
Garrido-Gil
Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Ana I
AI
Rodriguez-Perez
Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Patricia
P
Fernandez-Rodriguez
Neurosciences Division, CIMA, University of Navarra, Pamplona, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Jose L
JL
Lanciego
Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain. joseluis.labandeira@usc.es.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain. joseluis.labandeira@usc.es.
Jose L
JL
Labandeira-Garcia
D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008070:Lipopolysaccharides / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D018613:Microscopy, Confocal; D009434:Neural Pathways / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
C534933:Agt protein, rat; C544067:Agtr1a protein, rat; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D012083:Renin
Angiotensin; Basal ganglia; Dopamine; Neurodegeneration; Parkinson; Striatum