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research-article

PROBING MECHANICAL PROPERTIES OF BRAIN IN A TUBEROUS SCLEROSIS MODEL OF AUTISM

[+] Author and Article Information
Bo Qing

Department of Biological Engineering, MIT, Cambridge, MA, USA
bqing1@mit.edu

Elizabeth P. Canovic

Department of Materials Science and Engineering, MIT, Cambridge, MA, USA
canovic@mit.edu

Aleksandar S. Mijailovic

Department of Mechanical Engineering, MIT, Cambridge, MA, USA
amijailo@mit.edu

Anna Jagielska

Department of Materials Science and Engineering, MIT, Cambridge, MA, USA
aj58@mit.edu

Matthew J. Whitfield

Department of Materials Science and Engineering, MIT, Cambridge, MA, USA
mwhitfield16@gmail.com

Alexis L. Lowe

Department of Neuroscience, Wellesley College, Wellesley, MA, USA
alowe@wellesley.edu

Elyza H. Kelly

The F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
Elyza.Kelly@UTSouthwestern.edu

Daria Turner

The F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
dturner1213@comcast.net

Mustafa Sahin

The F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
Mustafa.Sahin@childrens.harvard.edu

Krystyn Van Vliet

Department of Biological Engineering, MIT, Cambridge, MA, USA; Department of Materials Science and Engineering, MIT, Cambridge, MA, USA
krystyn@mit.edu

1Corresponding author.

ASME doi:10.1115/1.4040945 History: Received November 28, 2017; Revised July 12, 2018

Abstract

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-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.

Copyright (c) 2018 by ASME
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