Article
Cellular evaluation of bone metabolism in autistic mouse model
Search Medline for
Authors
-
Julia Glaser
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Giessen, Germany
-
Deeksha Malhan
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Giessen, Germany
-
Julian Herfurth
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Giessen, Germany
-
Markus Rupp
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen and Marburg, Giessen, Germany
-
Fathi Hassan
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Giessen, Germany
-
Christian Bucher
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
-
Katharina Schmidt-Bleek
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
-
Thaqif El Khassawna
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Giessen, Germany
| Published: | October 22, 2019 |
|---|
Outline
Text
Objectives: Autism spectrum disorder (ASD) is a developmental disorder with a major impact on health care and finance systems. A possible co-regulation of the disease through bone cells can have potential therapeutic impact. Therefore, this study aims to characterize bone tissue in mouse models of ASD.
Methods: To assess the effect of autism on bone metabolism, knockout mouse models of Neuroligin 3 (NL3-/y, n=5) and Neuroligin 4 (NL4-/y, n=15) were compared with wild type (WT, n=12). After the establishment of autistic behaviour, whole body Dual X-ray Absorptiometry (DXA) was carried out. After euthanasia, long bones were collected followed by radiological, biomechanical, and histological analysis of hind limbs.
Results and conclusion: Whole body DXA showed slightly higher Bone Mineral Density (BMD) in NL4-/y (Mean ± SD: 0.077 ± 0.007) compared with WT (0.074 ± 0.0121). Fat% was significantly lower in NL4-/y compared with the WT (p=0.005). Tibiae BV/TV in µCT was higher in NL3-/y and NL4-/y (59.90 ± 4.669; 58.70 ± 5.895, respectively) compared with WT (55.31±4.075). Biomechanical testing revealed lower bending stiffness in NL3-/y (59.26 ± 10.850), and higher in NL4-/y (67.39 ± 8.800) compared with WT (63.36 ± 11.938). Movat Pentachrome stain of femora showed significantly lower non-mineralized matrix in NL3-/y when compared with NL4-/y (p = 0.011) and WT (p = 0.019). Higher trend of cartilaginous tissue area was seen in NL3-/y when compared with both WT and NL4-/y. Whereas, no difference in the calcified tissue area was seen between the groups. Although lower in both knockouts than WT, osteoclast activity assessment using TRAP enzymehistochemistry showed no significant difference between the groups.
ASD is a group of behavioural disorders clinically defined by significant function impairment. Neumeyer et al. 2015 reported the higher frequency of fractures with lower BMD among young adults with ASD. Moreover, the only approved drugs (risperidone and aripiprazole) are steroid-based and were reported to increase fracture risk. Yet, no previous study has addressed bone quality in autism preclinical models or patients. This study shows discrepancies in fat accumulation, bone density and cellular imbalance suggesting a regulatory role for bone cells in autism. Correlation between bone and neurodegenerative diseases is well established. In diseases such as neurofibromatosis and Alzheimer's, bone tissue management and mesenchymal cell therapy have shown promising effects. Currently we are addressing further serum and molecular bone parameters, and investigating monocytes populations in bone marrow to further analysis the correlation between autism and bone.
