PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM
© 2018 American Society of Mechanical Engineers (ASME). All rights reserved. Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical charac...
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| Format: | Article |
| Language: | English |
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ASME International
2021
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| Online Access: | https://hdl.handle.net/1721.1/135886 |
| _version_ | 1826215363074850816 |
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| author | Qing, Bo Canovic, Elizabeth P Mijailovic, Aleksandar S Jagielska, Anna Whitfield, Matthew J Lowe, Alexis L Kelly, Elyza H Turner, Daria Sahin, Mustafa Van Vliet, Krystyn J |
| author_facet | Qing, Bo Canovic, Elizabeth P Mijailovic, Aleksandar S Jagielska, Anna Whitfield, Matthew J Lowe, Alexis L Kelly, Elyza H Turner, Daria Sahin, Mustafa Van Vliet, Krystyn J |
| author_sort | Qing, Bo |
| collection | MIT |
| description | © 2018 American Society of Mechanical Engineers (ASME). All rights reserved. Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure. |
| first_indexed | 2024-09-23T16:25:53Z |
| format | Article |
| id | mit-1721.1/135886 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:25:53Z |
| publishDate | 2021 |
| publisher | ASME International |
| record_format | dspace |
| spelling | mit-1721.1/1358862022-04-01T16:18:08Z PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM Qing, Bo Canovic, Elizabeth P Mijailovic, Aleksandar S Jagielska, Anna Whitfield, Matthew J Lowe, Alexis L Kelly, Elyza H Turner, Daria Sahin, Mustafa Van Vliet, Krystyn J © 2018 American Society of Mechanical Engineers (ASME). All rights reserved. Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure. 2021-10-27T20:29:48Z 2021-10-27T20:29:48Z 2019 2019-09-24T17:57:29Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135886 en 10.1115/1.4040945 Journal of Biomechanical Engineering Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf ASME International ASME |
| spellingShingle | Qing, Bo Canovic, Elizabeth P Mijailovic, Aleksandar S Jagielska, Anna Whitfield, Matthew J Lowe, Alexis L Kelly, Elyza H Turner, Daria Sahin, Mustafa Van Vliet, Krystyn J PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title | PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title_full | PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title_fullStr | PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title_full_unstemmed | PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title_short | PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM |
| title_sort | probing mechanical properties of brain in a tuberous sclerosis model of autism |
| url | https://hdl.handle.net/1721.1/135886 |
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