Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice

• Published in: Journal of endocrinology Vol. 189; no. 3; pp. 617 - 627
• Main Authors: Svensson, J, Diez, M, Engel, J, Wass, C, Tivesten, Å, Jansson, J-O, Isaksson, O, Archer, T, Hökfelt, T, Ohlsson, C
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.06.2006; Portland Press
• Subjects: Aging; Aging - physiology; Alzheimer Disease; Alzheimer Disease - metabolism; Animal; Animals; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Immunohistochemistry; Immunohistochemistry - methods; In Situ Hybridization; Insulin-Like Growth Factor I; Insulin-Like Growth Factor I - metabolism; Knockout; Liver; Liver - metabolism; Maze Learning; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; Memory; metabolism; methods; Mice; Mice, Knockout; Models, Animal; Neurology; pharmacology; physiology; Poly I-C; Poly I-C - pharmacology; Regular papers; Nervous system diseases; Alzheimer disease; Memory; Rodentia; Gene expression; Insulin like growth factor 1; Learning; Vertebrata; Mammalia; Acquisition process; Mouse; Adult animal; Degenerative disease; Biological effect; Localization
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.1.06631

IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer’s disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I−/−), resulting in an approximately 80–85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I−/− and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I−/− mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF−/− mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I−/− mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I−/− mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.