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Below are descriptions of the Anatomy and Physiology grants that are currently active. To view a list of past grants in this area, please click on the link below.
Anatomy and Physiology - Past Grants |
Beth Israel Deaconess Medical Center , Boston , MA
2007-2010
Principal Investigator: Matthew Anderson, MD, Ph.D.
Innate Immunity and Thalamic Dysfunction in Autism
Sensory
processing defects are a prominent feature of autism with
descriptions of an over-reaction to noise, light, and touch
and increased pain thresholds. The thalamus is the gateway
of these sensory signals and recent reports indicate a marked
suppression of thalamic metabolic activity in autistic children.
Other studies reported excessive brain growth during the
early life. The cause of these functional and structural
brain abnormalities and resulting behavioral impairments
remain unknown. A clue may be the recent finding of inflammation-activated
glia in most autism brains. The inflammation was composed
of glial cell growth and peptide secretion. Neurons perform
the signal transmission and computations unique to the brain,
while glial cells support these neuron functions. Resting
glia provide structural and metabolic support to neurons
improving their signaling properties. The effect of inflammation-activated
glia on neurons is largely unknown. This project seeks answers
to this question to understand what influence the inflammation-activated
glia found in autism might have on the brain of individuals
suffering from autism.
The Laboratory of Matthew Anderson
Beth Israel Deaconess Medical Center, Boston, MA
2005-2008
Principal Investigator: Richard L. Sidman, M.D.
Stem Cell Injections Prevent Loss of Cerebellar Purkinje Neurons
The most consistent pathological abnormality found in autopsied cases of individuals with Autism Spectrum Disorder (ASD) is a decrease in number of cerebellar Purkinje neurons. Purkinje neurons are at risk in many neurological disorders, and undergo cell death in circumstances that may cause debilitating damage in other brain areas. The investigators’ belief that stem cells may help ASD patients comes from their experiments on mice with different neurogenetic disorders which cause selective destruction of Purkinje neurons. They injected neural stem cells (NSCs) into mouse cerebellum and found that mice injected with NSCs as babies, before Purkinje neurons were destined to die, grew up healthy, with cerebella that contained abundant Purkinje neurons. They established that stem cells had rescued the mouse’s Purkinje cells from dying! Before testing stem cell therapy in humans with brain disorders, the investigators must learn in mouse experiments what types of stem cells to use, how many cells to inject, how often, and by what routes, to maximize their distribution though affected brain regions with minimal discomfort. They have discovered that tissue plasminogen activator (tPA) is increased 10-fold in the cerebellum of one of their mouse mutants, and that tPA reverts to normal in mice they treated with NSCs. They plan to test the idea that tPA may act as a common “death mechanism” in many diseases affecting Purkinje neurons, and that therapy with stem cells should be directed at correcting the chemistry involved in this mechanism. The use of stem cells for rescue of Purkinje neurons would be of benefit regarding restoration of cerebellar function and may provide clues to chemical abnormalities that would lead to therapeutic recovery in brain regions that are more subtly affected in ASD, though with serious behavioral consequences.
Department of Neurology - Beth Israel Deaconess Medical Center
Boston University Medical School , Boston , MA
2007-2010
Principal Investigator: Gene J. Blatt, Ph.D.
Neuropathological and Neurochemical Analysis of Key Speech and Language Areas
in Autism
Autism is characterized by children and adults with a variety of
speech and language impairments. Brain imaging studies have
found that there is a different pattern of activation of
speech and language regions in the brains of those with
autism compared to normal controls in a variety of tasks.
Despite an abundance of structural and functional MRI findings,
there is a lack of information regarding the neurobiological
basis of these changes, i.e., characterizing the specific
cellular and neurochemical changes that may contribute to
alterations in cortical activation of speech and language
areas in autism. The investigator has therefore designed
a novel study investigating critical speech and language
areas in autistic brains, Broca's area and Wernicke's area
in the frontal and temporal lobes respectively compared
to adult age-matched controls. This investigation is designed
to detect specific alterations in the density and distribution
of key neuronal and glial types and in the neurotransmitter
receptor subtypes within the layered cortical areas. In
this way, the investigator can identify some of the core
neurobiological substrates that may in part underlie the
changes in language and social communication in autism.
This work may guide geneticists toward finding autism genes
and may guide the development of novel drug treatments.
The investigator will also determine via detection of activated
glia cells whether autism is a static process or a dynamic
process in the brain. This part of the study may lead the
investigator to identify the most vulnerable regions within
selected brain areas and may lead to a greater understanding
of ongoing cellular changes and their etiology.
Blatt Laboratory for Autism Research
Massachusetts Institute of Technology Media Laboratory, Cambridge , MA
2008-2010
Principal Investigators: Rosalind Picard, Sc.D. and Matthew Goodwin
Assessing and Communicating Movement Stereotypy and Arousal Telemetrically
in Individuals with Autism Spectrum Disorder
Stereotypical
motor movements or stereotypies are one of the most common
and least understood behaviors occurring in individuals
with Autism Spectrum Disorder (ASD). Stereotypies are complex
and thought to serve a multiplicity of functions. While
no one theory has obtained overwhelming support, there is
evidence for biological, operant, and homeostatic interpretations.
Of particular importance to the current project, a small
number of studies support the notion that there is a functional
relationship between movement stereotypy and arousal in
individuals with ASD, such that changes in autonomic activity
either precede or are a consequence of engaging in stereotypies.
Thus, it appears to be the case for some individuals that
stereotypic movements are adaptively employed to help regulate
stress, which in turn may help regulate attention, emotion,
and social behaviors. Unfortunately, it is difficult to
generalize these findings since previous studies fail to
report reliability statistics that demonstrate accurate
identification of movement stereotypy start and end times,
and use autonomic monitors that are obtrusive and thus only
suitable for short-term measurement in laboratory settings.
This project aims to explore the relationship between movement
stereotypy and autonomic activity in persons with ASD by
combining state-of-the-art ambulatory heart rate monitors
to objectively assess arousal across settings and wireless,
wearable motion sensors (accelerometers) and pattern recognition
software that can automatically and reliably detect stereotypical
motor movements in individuals with ASD in real-time. Obtaining
detailed and accurate information on the occurrence, type
of movement, frequency, duration, and setting events associated
with movement stereotypy is critical to understanding this
behavior. Moreover, assessing and communicating stereotypical
movements and arousal telemetrically may facilitate more
precise intervention efforts before they are entrenched
in an individual's repertoire.
MIT Media Lab
University of Cambridge Autism Research
Centre, Cambridge , UK
2004-2008
Principal Investigator: Simon Baron-Cohen, Ph.D.
Do Children with Autism Have Elevated Fetal Testosterone?
Neurologist, Norman Geschwind, suggested that fetal testosterone may
shape sex differences in brain development. Males produce
more of this because it is generated by the testes, but
females also produce it. Geschwind thought that the action
of fetal testosterone on the brain might explain why girls
tend to talk earlier than boys and why boys are overrepresented
in clinics for language disorders and conditions such as
autism. Human fetal testosterone can be measured through
a method called amniocentesis. In this study, amniotic fluid
taken from 3,000 women during their pregnancies will be
studied with respect to levels of fetal testosterone. Dr.
Baron-Cohen will determine how many of their children, who
are now 4 years or older, have been diagnosed with an autism
spectrum condition, or score highly on an autism spectrum
scale, and will test if these 'affected' children had abnormally
high levels of fetal testosterone. Earlier studies
in the general population have linked this hormone to social
and language development. It is important to investigate
whether it plays a role in the development of autism.
Autism
Research Centre
Simon
Baron-Cohen
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