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

Rebekah C. Evans, Ph.D., Georgetown University
In Vivo and Ex Vivo Dissection of Midbrain Neuron Activity During Exercise
Exercise is important for the health of the body and the mind. Exercise promotes learning and reduces symptoms of brain-related diseases such as Parkinson’s disease and Alzheimer’s disease. However, it…
William J. Giardino, Ph.D. Stanford University
Deciphering the Neuropeptide Circuitry of Emotional Arousal in Narcolepsy
This research project aims to investigate the neural mechanisms of a specific type of brain cell called neuropeptide neurons within a region of the brain’s amygdala network called the bed…
Howard Gritton, Ph.D., University of Illinois
Attention Mechanisms Contributing to Auditory Spatial Processing.
Our world is composed of a rich mixture of sounds. We often process sounds including speech in the presence of many other competing auditory stimuli (e.g., voices in a crowded…
Nora Kory, Ph.D., Harvard University
Elucidating the Fates and Functions of Lactate in the Brain
The human brain requires significant energy to function. Despite accounting for only 2% of our body weight, the brain consumes a substantial 20% of the body’s energy, relying on a…