Autism Spectrum Disorder

Insight from Dr. Penzes’ research will help scientists understand how connections in brain cells are disrupted in autism, and may uncover a viable therapeutic target that has real potential as an orally administered drug.
Autism spectrum disorder (ASD) is a physical condition that affects children at an alarmingly high rate. ASD includes autism, Asperger syndrome and Pervasive Development Disorder. One in 110 children will be diagnosed with autism. Abnormal social interaction, language difficulties and repetitive actions are all characteristics of autistic behavior. Autism also impairs a child’s ability to learn.
Exactly why autism occurs in one child and not another is unknown to scientists, although a combination of genetics and environment may play a role. Scientific evidence suggests that autism is caused by a malfunction of the connections, or synapses, between brain cells.
Recently, Peter Penzes, Ph.D., an associate professor of physiology at Northwestern University determined that a molecule, mutations in which have been genetically associated with autism, is involved in synapse development and remodeling in nerve cells.
Dr. Penzes will use his $40,000 BRF seed grant to further characterize the role of this molecule in mice. A strain of mice genetically engineered to be deficient in this molecule will be used to determine how such a shortage affects behavior, as well as brain physiology. Experiments will show how the molecule signals and regulates synapse development and behavior in a functioning organism. The research will also test predictions for how this molecule is associated with ASD. His research will focus on the frontal cortex, an area of the brain typically associated with psychiatric disorders, including ASD.
To study synapse development, Dr. Penzes will use fluorescent microscopy to observe and measure nerve cells in mouse brain slices. These cells will express a yellow fluorescent protein that will allow for the visualization of the connections between nerve cells.
The behavioral portion of the study will involve observing genetically altered mice that exhibit many of the social characteristics of autism without any unusual physical manifestations. Mice will be tested for how they exhibit core behaviors such as social interaction, nesting and juvenile play, as well as how they communicate. A variety of maze tests will assess learning capacity and response to change.
Insights from Dr. Penzes’ research will help scientists understand the electrical connections in brain cells that may be disrupted in autism cases. Understanding biological mechanisms that trigger autism can lead to the identification of potential targets for therapy. Targeting this molecule may be fruitful because it has a high likelihood of oral bioavailability and low toxicity in humans.
The knowledge realized through Dr. Penzes’ research may lead to better understanding of other neurodevelopmental disorders. Defects similar to the alterations in synapses prevalent in autism are also present in mental retardation, fragile-X syndrome and Down syndrome.
Using the data collected from his 2011 Seed Grant, Dr. Peter Penzes was able to turn this $40,000 grant into over $3 million in additional funding from the National Institute of Mental Health.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…