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Journal of Endocrinology (2006) 189, 617-627       DOI: 10.1677/joe.1.06631
© 2006 Society for Endocrinology
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Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice

J Svensson, M Diez1, J Engel2, C Wass2, Å Tivesten, J-O Jansson, O Isaksson, T Archer3, T Hökfelt1 and C Ohlsson

Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden
1 Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
2 Department of Pharmacology, Göteborg University, Göteborg, Sweden
3 Department of Psychology, Göteborg University, Göteborg, Sweden

(Requests for offprints should be addressed to J Svensson; Email: johan.svensson{at}medic.gu.se)

Conflicts of interest
O I is a co-founder of Tercica Inc, a company that produces IGF-I for use in children of short stature. No other author has any conflict of interest that would prejudice the impartiality of this scientific work.

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.




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