Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression

Freus N, Wank I, Häfele M, Kalinichenko L, Müller CP, Strobelt S, Ludwig A, Heß A, Kreitz S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 15

Article Number: 10116

Journal Issue: 1

DOI: 10.1038/s41598-025-95000-2

Abstract

Osteocalcin (OCN) is an endocrine hormone that signals in the periphery, regulating male fertility, energy expenditure and glucose homeostasis. It can also cross the blood-brain-barrier and act on the brain via receptors GPR37 and GPR158. In the brain, OCN influences neurotransmitter synthesis of serotonin, norepinephrine, and dopamine. OCN’s function is related to cognitive and memory performance and lack of OCN is associated with anxiety and depression-like behavior in mice. We used multiparametric magnetic resonance imaging (MRI) including pharmacological MRI and resting state functional MRI, along with gene expression data for Gpr37 and Gpr158 to investigate the physiological effects of intravenously administered OCN on the wild type mouse brain. We found four core brain regions (brainstem, limbic output, association cortex, and basal ganglia) that are highly relevant in all three analytical modalities (i.e. pharmacological, resting state MRI and gene expression) and play therefore a major role in mediating OCN’s effect in the brain. This study provides the first imaging data of the physiological impact of OCN on the mouse brain, suggesting its potential role in modulating brain function and its relevance as a candidate for further investigation in anxiety, depression, and cognitive impairments.

Authors with CRIS profile

Natalia Freus Medizinische Fakultät Isabel Wank Institut für Experimentelle und Klinische Pharmakologie und Toxikologie Maximilian Häfele Lehrstuhl für Pharmakologie und Toxikologie Liubov Kalinichenko Department of Psychiatry and Psychotherapy Peter Christian Müller Professur für Suchtmedizin Sandra Strobelt Lehrstuhl für Pharmakologie und Toxikologie Andreas Ludwig Lehrstuhl für Pharmakologie und Toxikologie Andreas Heß Lehrstuhl für Pharmakologie und Toxikologie Silke Kreitz Lehrstuhl für Pharmakologie und Toxikologie

Additional Organisation(s)

FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

How to cite

APA:

Freus, N., Wank, I., Häfele, M., Kalinichenko, L., Müller, C.P., Strobelt, S.,... Kreitz, S. (2025). Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-95000-2

MLA:

Freus, Natalia, et al. "Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression." Scientific Reports 15.1 (2025).

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