Insulin receptors in mouse brain: Reversibility of age-related impairments by a thymic extract

Abstract

Recently, we have shown that insulin receptors (InsRs) in the brain undergo impairments with aging. Interestingly, age-related alterations of brain InsRs, are not irreparable as thymus grafts are able to recover them. With the present study we verified the possibility that an aqueous extract from calf thymus (TME) can mimic the restoring action of age-related impairments induced by thymus graft. InsR characteristics were assayed in a group of 25 months old BALB/c-nu mice treated with TME: 2μg/g body weight every third day, for total five subcutaneous injections. The last dose was injected the day before animals were killed. Other two groups of young (4 months) and old (25 months) mice received saline solution with the same schedule. A two-sites model analysis of receptor data confirms the age-dependent decrease of InsR number and kd previously observed in the high affinity population. Furthermore, a statistically significant recovery of number impairment is shown in TME-treated animals. On the contrary, the characteristics of the low affinity receptor subset show no statistically significant differences among the three animal models studied. TME induced recovery of the age-related changes found in brain InsRs, together with previously observed regulatory action of the same thymic extract on the adrenergic system, suggest that thymic gland does not necessarily have to mutually interact with other controlling systems for maintaining or recoving homeostasis of the complex neuroendocrine network during development and aging.

Characterization of aged male BALB/ccenp mice as a model of dementia

“…Rodents have a leading role in animal models of dementia and among the most used strains by researchers studying cognitive disorders are C57BL/6 [13] and SAMP8 [14]. In the case of the BALB/c strain there are few studies where it was used aged mice as a model of dementia [15].…”

“…There is no reference to the characterization of a dementia model in aged mice of the BALB/c strain, even though it's widely used in behavioural studies related to stress, fear and cognitive function [16][17][18]. On the other hand, among the models of aged mice described for dementia there is variability about the minimum age at which behavioural, pathological or biochemical symptoms of the disease take place [13][14][15]. In all of these models there is great variety about the minimal age at which behavioural, pathological or biochemical symptoms of the disease appear.…”