Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression
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 synthe...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-95000-2 |
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| author | Natalia K. Freus Isabel Wank Maximilian Häfele Liubov S. Kalinichenko Christian P. Müller Sandra Strobelt Andreas Ludwig Andreas Hess Silke Kreitz |
| author_facet | Natalia K. Freus Isabel Wank Maximilian Häfele Liubov S. Kalinichenko Christian P. Müller Sandra Strobelt Andreas Ludwig Andreas Hess Silke Kreitz |
| author_sort | Natalia K. Freus |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-17d050635a034e23a04427f07d029755 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-17d050635a034e23a04427f07d0297552025-08-20T02:49:32ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-95000-2Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expressionNatalia K. Freus0Isabel Wank1Maximilian Häfele2Liubov S. Kalinichenko3Christian P. Müller4Sandra Strobelt5Andreas Ludwig6Andreas Hess7Silke Kreitz8Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergDepartment of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-NurembergDepartment of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-NurembergAbstract 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.https://doi.org/10.1038/s41598-025-95000-2OsteocalcinMouse fMRIFunctional connectivityrCBVDepressionAllen brain atlas |
| spellingShingle | Natalia K. Freus Isabel Wank Maximilian Häfele Liubov S. Kalinichenko Christian P. Müller Sandra Strobelt Andreas Ludwig Andreas Hess Silke Kreitz Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression Scientific Reports Osteocalcin Mouse fMRI Functional connectivity rCBV Depression Allen brain atlas |
| title | Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression |
| title_full | Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression |
| title_fullStr | Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression |
| title_full_unstemmed | Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression |
| title_short | Pharmacological and resting state fMRI reveal Osteocalcin’s effects on mouse brain regions with high Gpr37 and Gpr158 expression |
| title_sort | pharmacological and resting state fmri reveal osteocalcin s effects on mouse brain regions with high gpr37 and gpr158 expression |
| topic | Osteocalcin Mouse fMRI Functional connectivity rCBV Depression Allen brain atlas |
| url | https://doi.org/10.1038/s41598-025-95000-2 |
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