Liver-derived IGF-I regulates exploratory activity in old mice

Area of Science:

• Endocrinology
• Neuroscience
• Gerontology

Background:

• Growth hormone (GH) replacement therapy enhances well-being and initiative in hypopituitary patients.
• Experimental data suggest GH's psychic effects may correlate with increased locomotor activity in mice.
• The precise mediation of these effects, whether by GH directly or by circulating IGF-I, remains unclear.

Purpose of the Study:

• To investigate the role of liver-derived insulin-like growth factor-I (IGF-I) in mediating the effects of growth hormone (GH) on locomotor and exploratory activity in mice.
• To determine if reduced circulating IGF-I levels impact habituation processes and anxiety levels in aging mice.

Main Methods:

• Utilized liver-specific IGF-I knockout mice (LI-IGF-I-/-) with significantly reduced circulating IGF-I and elevated GH secretion.
• Assessed locomotor activity using activity boxes across different age groups (6, 14, and 20 months).
• Measured anxiety levels using the elevated plus-maze test.

Main Results:

• Younger LI-IGF-I-/- mice (6 months) showed activity levels comparable to controls.
• Older LI-IGF-I-/- mice (14 and 20 months) exhibited a significant decrease in horizontal and rearing activity.
• Aged LI-IGF-I-/- mice displayed an altered habituation process, with no significant changes in anxiety levels.

Conclusions:

• Liver-derived IGF-I plays a crucial role in maintaining normal levels of exploratory and locomotor activity in aging mice.
• The findings suggest that IGF-I mediates at least a portion of growth hormone's effects on exploratory behavior.
• Reduced IGF-I impacts habituation but not anxiety levels in aged mice.