Short-time recognition memory assessment in agouti-mutant A^y/a mice

Introduction. Obesity and its complications are a leading medical and social problem in Russia and worldwide. The agouti-mutant A^y/a mice are used as a model of monogenic obesity caused by a suppression of the melanocortin system. The so-called melanocortin syndrome includes not only a variety of metabolic abnormalities but also a number of neurocognitive alterations, which have been relatively little studied.

Aim. Our objective was to assess the short-term recognition memory in male and female A^y/a mice compared to wild-type littermates.

Materials and methods. The experiments were carried out on 8 male and 7 female C57Bl/6- A^y/a mice along with 8 male and 7 female wild-type (C57Bl/6-a/a) littermates, aged 1 year. Recognition memory was assessed via sequential testing in the "Novel object recognition", "Novel object location", "Object-in-Place" (OiP), and "Object recency discrimination" (ORD) tests with a 5 min- and 3 day-long intervals between the testing phases and between the tests themselves, respectively. For each of the tests, we calculated the discrimination index (DI) using a conventional formula.

Results and discussion. Wild-type mice of both sexes demonstrated positive DI values in all of the tests. A^y/a males performed comparably with their wild-type littermates in all of the tests, while A^y/a females had significantly lower mean DI values in the OiP and ORD tests (p < 0.05 for both). These results may reflect an impairment of allocentric spatial memory and associative recognition, which may indicate damage to the medial prefrontal cortex, the medial dorsal nucleus and/or nucleus reuniens of the thalamus. The presence of such deficit in A^y/a females exclusively may be related to greater severity of systemic and central metabolic abnormalities, insulin resistance, and oxidative stress.

Сonclusion. In this study, we found an impairment of higher-level aspects of short-term recognition memory in female agouti-mutant C57Bl/6- A^y/a mice. The state of other types of memory, sex- and age-specific differences and dynamics of memory deficits in A^y/a mice require further elucidation. The distinct features of short-term recognition memory in male and female A^y/a mice need to be taken into consideration when planning and conducting preclinical trials.

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