Elsevier

Neuroscience

Volume 80, Issue 4, 11 August 1997, Pages 1033-1040
Neuroscience

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

https://doi.org/10.1016/S0306-4522(97)00154-1Get rights and content

Abstract

The insulin-like growth factors (IGF-I and IGF-II) and insulin are localized within distinct brain regions and their respective functions are mediated by specific membrane receptors. High densities of binding sites for these growth factors are discretely and differentially distributed throughout the brain, with prominent levels localized to the hippocampal formation. IGFs and insulin, in addition to their growth promoting actions, are considered to play important roles in the development and maintenance of normal cell functions throughout life. We compared the anatomical distribution and levels of IGF and insulin receptors in young (five month) and aged (25 month) memory-impaired and memory-unimpaired male Long–Evans rats as determined in the Morris water maze task in order to determine if alterations in IGF and insulin activity may be related to the emergence of cognitive deficits in the aged memory-impaired rat. In the hippocampus, [125I]IGF-I receptors are concentrated primarily in the dentate gyrus (DG) and the CA3 sub-field while high amounts of [125I]IGF-II binding sites are localized to the pyramidal cell layer, and the granular cell layer of the DG. [125I]insulin binding sites are mostly found in the molecular layer of the DG and the CA1 sub-field. No significant differences were found in [125I]IGF-I, [125I]IGF-II or [125I]insulin binding levels in any regions or laminae of the hippocampus of young vs aged rats, and deficits in cognitive performance did not relate to altered levels of these receptors in aged memory-impaired vs aged memory-unimpaired rats. Other regions, including various cortical areas, were also examined and failed to reveal any significant differences between the three groups studied.

It thus appears that IGF-I, IGF-II and insulin receptor sites are not markedly altered during the normal ageing process in the Long–Evans rat, in spite of significant learning deficits in a sub-group (memory-impaired) of aged animals. Hence, recently reported changes in IGF-I receptor messenger RNA levels in aged memory-impaired rats[42]are apparently not reflected at the level of the translated protein.

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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