Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice

Sheila Leone, Rugia Shohreh, Fabio Manippa, Lucia Recinella, Claudio Ferrante, Giustino Orlando, Roberto Salvatori, Michele Vacca, Luigi Brunetti

Research output: Contribution to journalArticle

Abstract

Objective: GH-releasing hormone (GHRH) is a key regulator of GH secretion. The role of GH in anxiety is somewhat contradictory. The aim of this study is to elucidate the consequences of lack of GHRH on emotional behaviour in a mouse model of GH deficiency due to removal of the GHRH gene (GHRH knock out, GHRHKO). Design: Homozygous GHRHKO and wild type male mice were utilized for this study. The emotional behaviour was measured through a battery of behavioural tests (locomotor activity/open field, light-dark exploration, elevated plus maze, forced swim test, tail suspension test). To correlate the emotional behaviour with brain neurochemistry, we evaluated thyrotropin-releasing hormone (TRH) gene expression in hypothalamic tissue by real-time PCR, and the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in prefrontal cortex by HPLC analysis. Results: GHRHKO mice showed increased exploratory activity. In the open field test (P<0.005), light-dark box (P<0.005) and elevated plus maze (P<0.05), GHRHKO mice demonstrated a decrease in anxiety-related behaviour. In addition, GHRHKO mice showed reduced immobility time with respect to control in forced swim test and tail suspension test (P<0.0001). The gene expression of hypothalamic TRH (P<0.05) was increased, while NE levels in prefrontal cortex were decreased compared to control (P<0.05). Conclusion: These results suggest that in male mice GHRH deficiency brings about an increased physical activity and decreased anxiety- and depression-related behaviour, possibly related to increased TRH and decreased NE levels in the brain.

Original languageEnglish (US)
Pages (from-to)192-197
Number of pages6
JournalGrowth Hormone and IGF Research
Volume24
Issue number5
DOIs
StatePublished - Oct 1 2014

Fingerprint

Growth Hormone-Releasing Hormone
Knockout Mice
Thyrotropin-Releasing Hormone
Hindlimb Suspension
Norepinephrine
Anxiety
Prefrontal Cortex
Serotonin
Pituitary Hormone-Releasing Hormones
Neurochemistry
Gene Expression
Light
Brain
Locomotion
Real-Time Polymerase Chain Reaction
Dopamine
High Pressure Liquid Chromatography
Hormones
Depression
Genes

Keywords

  • Anxiety
  • Depression
  • Growth hormone-releasing hormone knockout
  • Norepinephrine
  • Thyrotropin-releasing hormone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Leone, S., Shohreh, R., Manippa, F., Recinella, L., Ferrante, C., Orlando, G., ... Brunetti, L. (2014). Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice. Growth Hormone and IGF Research, 24(5), 192-197. https://doi.org/10.1016/j.ghir.2014.06.004

Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice. / Leone, Sheila; Shohreh, Rugia; Manippa, Fabio; Recinella, Lucia; Ferrante, Claudio; Orlando, Giustino; Salvatori, Roberto; Vacca, Michele; Brunetti, Luigi.

In: Growth Hormone and IGF Research, Vol. 24, No. 5, 01.10.2014, p. 192-197.

Research output: Contribution to journalArticle

Leone, S, Shohreh, R, Manippa, F, Recinella, L, Ferrante, C, Orlando, G, Salvatori, R, Vacca, M & Brunetti, L 2014, 'Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice', Growth Hormone and IGF Research, vol. 24, no. 5, pp. 192-197. https://doi.org/10.1016/j.ghir.2014.06.004
Leone, Sheila ; Shohreh, Rugia ; Manippa, Fabio ; Recinella, Lucia ; Ferrante, Claudio ; Orlando, Giustino ; Salvatori, Roberto ; Vacca, Michele ; Brunetti, Luigi. / Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice. In: Growth Hormone and IGF Research. 2014 ; Vol. 24, No. 5. pp. 192-197.
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abstract = "Objective: GH-releasing hormone (GHRH) is a key regulator of GH secretion. The role of GH in anxiety is somewhat contradictory. The aim of this study is to elucidate the consequences of lack of GHRH on emotional behaviour in a mouse model of GH deficiency due to removal of the GHRH gene (GHRH knock out, GHRHKO). Design: Homozygous GHRHKO and wild type male mice were utilized for this study. The emotional behaviour was measured through a battery of behavioural tests (locomotor activity/open field, light-dark exploration, elevated plus maze, forced swim test, tail suspension test). To correlate the emotional behaviour with brain neurochemistry, we evaluated thyrotropin-releasing hormone (TRH) gene expression in hypothalamic tissue by real-time PCR, and the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in prefrontal cortex by HPLC analysis. Results: GHRHKO mice showed increased exploratory activity. In the open field test (P<0.005), light-dark box (P<0.005) and elevated plus maze (P<0.05), GHRHKO mice demonstrated a decrease in anxiety-related behaviour. In addition, GHRHKO mice showed reduced immobility time with respect to control in forced swim test and tail suspension test (P<0.0001). The gene expression of hypothalamic TRH (P<0.05) was increased, while NE levels in prefrontal cortex were decreased compared to control (P<0.05). Conclusion: These results suggest that in male mice GHRH deficiency brings about an increased physical activity and decreased anxiety- and depression-related behaviour, possibly related to increased TRH and decreased NE levels in the brain.",
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AU - Orlando, Giustino

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