Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals
Body weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, t...
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3779 |
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| author | Libo Yu-Taeger Arianna Novati Jonasz Jeremiasz Weber Elisabeth Singer-Mikosch Ann-Sophie Pabst Fubo Cheng Carsten Saft Jennifer Koenig Gisa Ellrichmann Taneli Heikkinen Mahmoud A. Pouladi Olaf Riess Huu Phuc Nguyen |
| author_facet | Libo Yu-Taeger Arianna Novati Jonasz Jeremiasz Weber Elisabeth Singer-Mikosch Ann-Sophie Pabst Fubo Cheng Carsten Saft Jennifer Koenig Gisa Ellrichmann Taneli Heikkinen Mahmoud A. Pouladi Olaf Riess Huu Phuc Nguyen |
| author_sort | Libo Yu-Taeger |
| collection | DOAJ |
| description | Body weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, these changes could be due to abnormal tissue growth rather than tissue atrophy. Moreover, BW and BMI are reported to be more affected in males than females in HD animal models and patients. Here, we confirmed sex-dependent growth alterations in the BACHD rat model for HD and investigated the associated contributing factors. Our results showed growth abnormalities along with decreased plasma testosterone and insulin-like growth factor 1 (IGF-1) levels only in males. Moreover, we demonstrated correlations between growth parameters, IGF-1, and testosterone. Our analyses further revealed an aberrant transcription of testosterone biosynthesis-related genes in the testes of BACHD rats with undisturbed luteinizing hormone (LH)/cAMP/PKA signaling, which plays a key role in regulating the transcription process of some of these genes. In line with the findings in BACHD rats, analyses in the R6/2 mouse model of HD showed similar results. Our findings support the view that mutant huntingtin may induce abnormal growth in males via the dysregulation of gene transcription in the testis, which in turn can affect testosterone biosynthesis. |
| first_indexed | 2024-03-09T17:51:04Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:04Z |
| publishDate | 2022-11-01 |
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| series | Cells |
| spelling | doaj.art-182d9543377f43cc8144fbbfc702c74e2023-11-24T10:43:40ZengMDPI AGCells2073-44092022-11-011123377910.3390/cells11233779Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease AnimalsLibo Yu-Taeger0Arianna Novati1Jonasz Jeremiasz Weber2Elisabeth Singer-Mikosch3Ann-Sophie Pabst4Fubo Cheng5Carsten Saft6Jennifer Koenig7Gisa Ellrichmann8Taneli Heikkinen9Mahmoud A. Pouladi10Olaf Riess11Huu Phuc Nguyen12Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, GermanyInstitute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, GermanyInstitute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, GermanyDepartment of Neurology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Neurology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Neurology, Ruhr University Bochum, 44801 Bochum, GermanyCharles River Discovery Services, 70210 Kuopio, FinlandDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeInstitute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, GermanyDepartment of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, GermanyBody weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, these changes could be due to abnormal tissue growth rather than tissue atrophy. Moreover, BW and BMI are reported to be more affected in males than females in HD animal models and patients. Here, we confirmed sex-dependent growth alterations in the BACHD rat model for HD and investigated the associated contributing factors. Our results showed growth abnormalities along with decreased plasma testosterone and insulin-like growth factor 1 (IGF-1) levels only in males. Moreover, we demonstrated correlations between growth parameters, IGF-1, and testosterone. Our analyses further revealed an aberrant transcription of testosterone biosynthesis-related genes in the testes of BACHD rats with undisturbed luteinizing hormone (LH)/cAMP/PKA signaling, which plays a key role in regulating the transcription process of some of these genes. In line with the findings in BACHD rats, analyses in the R6/2 mouse model of HD showed similar results. Our findings support the view that mutant huntingtin may induce abnormal growth in males via the dysregulation of gene transcription in the testis, which in turn can affect testosterone biosynthesis.https://www.mdpi.com/2073-4409/11/23/3779Huntington diseasemusculoskeletal growthbrain growthsex-differenceBACHD ratsR6/2 mice |
| spellingShingle | Libo Yu-Taeger Arianna Novati Jonasz Jeremiasz Weber Elisabeth Singer-Mikosch Ann-Sophie Pabst Fubo Cheng Carsten Saft Jennifer Koenig Gisa Ellrichmann Taneli Heikkinen Mahmoud A. Pouladi Olaf Riess Huu Phuc Nguyen Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals Cells Huntington disease musculoskeletal growth brain growth sex-difference BACHD rats R6/2 mice |
| title | Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals |
| title_full | Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals |
| title_fullStr | Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals |
| title_full_unstemmed | Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals |
| title_short | Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals |
| title_sort | evidences for mutant huntingtin inducing musculoskeletal and brain growth impairments via disturbing testosterone biosynthesis in male huntington disease animals |
| topic | Huntington disease musculoskeletal growth brain growth sex-difference BACHD rats R6/2 mice |
| url | https://www.mdpi.com/2073-4409/11/23/3779 |
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