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Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-Running Activity in Rats.

Mai Otsuka¹, Yu Takeuchi¹, Maho Moriyama¹

¹Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.

|June 5, 2025

Summary

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Neuromedin U (NMU) regulates motivated activity in male rats by influencing daily testosterone cycles. NMU knockout rats showed reduced activity linked to disrupted testosterone rhythms.

Area of Science:

Neuroendocrinology
Behavioral Neuroscience
Reproductive Biology

Background:

Endogenous Neuromedin U (NMU) function is not fully understood.
NMU signaling pathways are implicated in various physiological processes.
Disruptions in daily rhythms can impact behavior and hormone levels.

Purpose of the Study:

To investigate the role of endogenous NMU in regulating motivated behavior in rats.
To determine the impact of NMU knockout (KO) on physical activity and hormonal profiles.
To elucidate the mechanisms underlying NMU's influence on behavior.

Main Methods:

Generation and analysis of NMU knockout (KO) rats compared to wildtype (WT).
Assessment of wheel-running and home cage activity.

Keywords:

Neuromedin U activity motivation rat testosterone wheel-running

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Measurement of plasma testosterone levels and luteinizing hormone beta subunit (Lhb) mRNA expression.

Immunostaining for luteinizing hormone (LH)-expressing cells.

Main Results:

Male NMU KO rats exhibited significantly decreased wheel-running activity compared to WT rats.
NMU KO rats showed a lack of diurnal variation in plasma testosterone levels.
Testosterone administration restored wheel-running activity in NMU KO rats.
Reduced Lhb mRNA expression and smaller LH-expressing cells were observed in NMU KO rats.

Conclusions:

Endogenous NMU plays a crucial role in regulating motivated activity in male rats.
NMU influences motivated behavior through the regulation of diurnal testosterone rhythms.
NMU signaling impacts the hypothalamic-pituitary-gonadal axis, affecting LH release and testosterone secretion.