Behavioural phenotyping, learning and memory in young and aged growth hormone-releasing hormone-knockout mice

Background: Growth hormone-releasing hormone (GHRH) plays an important role in brain functions. The aim of this study was to examine cognitive functions and emotional behaviour in a mouse model of isolated GH deficiency due to bi-allelic ablation of the GHRH gene (GHRH knockout, GHRHKO). Methods: Learning, memory and emotional behaviour were evaluated using a series of validated tests (Morris water maze, eight-arm radial maze, open field, elevated plus maze test, forced swim tests) in 2-, 5- and 12-month-old male mice either homozygous (-/-) or heterozygous (+/-) for the GHRHKO allele. Results: Compared with age-matched +/- mice, -/- mice showed decreased cognitive performance in Morris water maze and eight-arm radial maze tests. By comparing the effects of aging in each genotype, we observed an age-related impairment in test results in +/- mice, while in -/- mice a significant decline in cognitive function was found only in 12 months compared with 2-month-old mice, but no difference was found between 5 months old vs 2 months old. -/- mice showed increased exploration activity compared to age-matched +/- controls, while both strains of mice had an age-related decrease in exploration activity. When evaluated through open field, elevated plus maze and forced swim tests, -/- mice demonstrated a decrease in anxiety and depression-related behaviour compared to age-matched +/- controls. Conclusions: Our results suggest that homozygous ablation of GHRH gene is associated with decreased performance in learning and memory tests, possibly linked to increased spontaneous locomotor activity. In addition, we observed an age-related decline in cognitive functions in both genotypes.