Sheila Leone1, Lucia Recinella2, Annalisa Chiavaroli3, Claudio Ferrante4, Giustino Orlando5, Michele Vacca6, Roberto Salvatori7, Luigi Brunetti8. 1. S Leone, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. 2. L Recinella, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. 3. A Chiavaroli, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. 4. C Ferrante, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. 5. G Orlando, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy gorlando@unich.it. 6. M Vacca, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. 7. R Salvatori, Endocrinology, Johns Hopkins University, Baltimore, 21287, United States. 8. L Brunetti, Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
Abstract
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 months 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 and eight-arm radial maze tests. By comparing the effects of aging in each genotype, we observed an age-related impairment in +/- mice, while in -/- mice a significant decline in cognitive function was found only in 12 months compared with 2 months 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: Homozygous ablation of GHRH gene is associated with decreased performance in learning and memory tests, possibly linked to increased spontaneous locomotor activity. Additionally, we observed an age-related decline in cognitive functions in both genotypes.
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 months 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 and eight-arm radial maze tests. By comparing the effects of aging in each genotype, we observed an age-related impairment in +/- mice, while in -/- mice a significant decline in cognitive function was found only in 12 months compared with 2 months 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: Homozygous ablation of GHRH gene is associated with decreased performance in learning and memory tests, possibly linked to increased spontaneous locomotor activity. Additionally, we observed an age-related decline in cognitive functions in both genotypes.
Authors: P S van Dam; A Aleman; W R de Vries; J B Deijen; E A van der Veen; E H de Haan; H P Koppeschaar Journal: Growth Horm IGF Res Date: 2000-04 Impact factor: 2.372
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