title: Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging.
abstract: The local renin-angiotensin system (RAS) and insulin-like growth factor 1 (IGF-1) have been involved in longevity, neurodegeneration and aging-related dopaminergic degeneration. However, it is not known whether IGF-1 and angiotensin-II (AII) activate each other. In the present study, AII, via type 1 (AT1) receptors, exacerbated neuroinflammation and dopaminergic cell death. AII, via AT1 receptors, also increased the levels of IGF-1 and IGF-1 receptors in microglial cells. IGF-1 inhibited RAS activity in dopaminergic neurons and glial cells, and also inhibited the AII-induced increase in markers of the M1 microglial phenotype. Consistent with this, IGF-1 decreased dopaminergic neuron death induced by the neurotoxin MPP+ both in the presence and in the absence of glia. Intraventricular administration of AII to young rats induced a significant increase in IGF-1 expression in the nigral region. However, aged rats showed decreased levels of IGF-1 relative to young controls, even though RAS activity is known to be enhanced in aged animals. The study findings show that IGF-1 and the local RAS interact to inhibit or activate neuroinflammation (i.e. transition from the M1 to the M2 phenotype), oxidative stress and dopaminergic degeneration. The findings also show that this mechanism is impaired in aged animals.
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rodriguez-Perez
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Borrajo
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Diaz-Ruiz
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garrido-Gil
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Labandeira-Garcia
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D061251:Primary Cell Culture; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D044140:Receptor, Angiotensin, Type 1; C548904:insulin-like growth factor-1, rat; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D015655:1-Methyl-4-phenylpyridinium
keywords: Gerotarget; IGF-1; Parkinson; longevity; microglia; neurodegeneration