Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice.
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.
Svensson
J
J
Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. johan.svensson@medic.gu.se
Diez
M
M
Engel
J
J
Wass
C
C
Tivesten
A
A
Jansson
J-O
JO
Isaksson
O
O
Archer
T
T
Hökfelt
T
T
Ohlsson
C
C
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011070:Poly I-C / Q000494:pharmacology
D007334:Insulin-Like Growth Factor I; D011070:Poly I-C