Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats
Section snippets
Animals
All animals used in this study were obtained from our colony of aged Long–Evans rats purchased at young adult ages (five months; males) from Charles River (St Constant, Quebec, Canada). Animals were maintained on a 12 h light-dark cycle in temperature- and humidity-controlled rooms, and fed standard laboratory chow with access to water ad libitum. Animal care was according to protocols and guidelines approved by the McGill University Animal Care Committee and the Canadian Council for Animal
Morris water swim maze task
Aged animals screened using the Morris water swim maze were divided into two major subgroups (Fig. 1). Aged-cognitively impaired (AI) animals represented approximately 36% of the population. AU animals were 39% and the remainder fell in between these two main subgroups.
In vitro receptor autoradiography
As reported earlier using receptor autoradiography,24, 28a widespread distribution of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites was noted throughout the rat brain, especially in the hippocampal formation.
Discussion
No significant differences were found in [125I]IGF-I, [125I]IGF-II or [125I]insulin receptor levels in any sub-fields of the hippocampus of young and aged rats. Furthermore, deficits in cognitive performance did not relate to alterations in the level of these receptors in AI compared to AU rats. Other regions, including various cortical areas, the amygdaloid complex and the posterior hypothalamus were also examined and failed to reveal significant differences. It thus appears that IGF-I, IGF-II
Conclusion
In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and intraperitoneal glucose treatment can result in improved learning performance.[29]In aged cognitively-impaired Wistar rats, significantly reduced cerebral glucose utilization was observed in different brain regions associated with learning and memory processes.[49]Severe decreases in brain insulin levels were also observed in aged rabbits,[41]and the expression of the glucose transporters
Acknowledgements
This work was supported by the Medical Research Council of Canada. S. D. is a Post-Doctoral Fellow of the Alzheimer Society of Canada. W. R. holds a studentship from the “Fonds pour la formation des chercheurs et l'aide à la recherche du Québec”. R. Q. and S. K. are “Chercheurs boursiers” from the “Fonds de la recherche en santé du Québec”. The authors would like to thank the helpful contribution of Jean-Guy Chabot from the Douglas Hospital Research Centre. Preliminary data will be presented at
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