Insulin and insulin-like growth factor-I receptors in astrocytes exert different effects on behavior and Alzheimer´s-like pathology [version 3; peer review: 2 approved]

• Published in: F1000Research
• Main Authors: Raquel Herrero-Labrador, Jansen Fernandes, Ana M. Fernandez, Laura Martinez-Rachadell, Ignacio Torres Aleman, Jonathan Zegarra-Valdivia
• Format: Article
• Language: English
• Published: F1000 Research Ltd 2022-12-01
• Subjects: Astrocytes; Alzheimer`s disease; Insulin; Insulin-like growth factor I; Glial cells.; eng
• Online Access: https://f1000research.com/articles/11-663/v3

Background: Pleiotropic actions of insulin and insulin-like growth factor I (IGF-I) in the brain are context- and cell-dependent, but whether this holds for their receptors (insulin receptor (IR) and IGF-I receptor (IGF-IR), respectively), is less clear. Methods: We compared mice lacking IR or IGF-IR in glial fibrillary astrocytic protein (GFAP)-expressing astrocytes in a tamoxifen-regulated manner, to clarify their role in this type of glial cells, as the majority of data of their actions in brain have been obtained in neurons. Results: We observed that mice lacking IR in GFAP astrocytes (GFAP IR KO mice) develop mood disturbances and maintained intact cognition, while at the same time show greater pathology when cross-bred with APP/PS1 mice, a model of familial Alzheimer´s disease (AD). Conversely, mice lacking IGF-IR in GFAP astrocytes (GFAP-IGF-IR KO mice) show cognitive disturbances, maintained mood tone, and show control-dependent changes in AD-like pathology. Conclusions: These observations confirm that the role of IR and IGF-IR in the brain is cell-specific and context-dependent.