Who’s new at OHSU? Marina Guizzetti, Ph.D.

Marina Guizzetti, Ph.D., is an associate professor in the Department of Behavioral Neuroscience at OHSU and a research biologist with the Portland VA Health Care System. Her research focuses on the neurodevelopmental effects of alcohol on the developing brain, specifically looking at Fetal Alcohol Spectrum Disorders.

Marina Guizzetti and family
Marina Guizzetti and family

Where are you from originally?
I’m from northern Italy and also where I was educated. I got my degree at the University of Pavia just south of Milan. This is the same university from which Camillo Golgi, who won the Nobel Prize in 1906 for his work on the structure of the nervous system, graduated and worked for most of his career. Among other things, he discovered a technique for staining brain tissue he called “reazione nera” (black reaction) that’s still in use today. I completed my Ph.D. at the University of Milan. In 1994, I moved to Seattle to do my postdoc at the University of Washington. I was there for six years as a postdoc and another 10 years as a research scientist. I then moved to the University of Illinois in Chicago to take a position as associate professor and was there for about five years before coming to OHSU in February.

What brought you to OHSU?
My predecessor in this position retired, and I was approached by the VA and OHSU’s Department of Behavioral Neuroscience to replace her, as our research was well aligned. The department has a very large program on alcohol research, and I have been working in this field since I came to the U.S. in 1994. It was a good fit.

What is the primary focus of your research?
Since my time at the University of Washington, my work has focused on the cellular mechanisms involved in the neurodevelopmental effects of alcohol on the developing brain underlying Fetal Alcohol Spectrum Disorders, or FASD. In utero alcohol exposure causes a wide range of developmental effects including Fetal Alcohol Syndrome at the most extreme end of the spectrum.

While I’m now working in the Department of Behavioral Neuroscience, I’m actually a cell biologist by training and love the mechanistic aspect of neuroscience research. I’m particularly interested in glial cells and their role in modulating neuronal development and function. The word glia is derived from ancient Greek and literally means “glue.” When these cells were first discovered, they were thought to do nothing other than keep neurons in place. But in the last 20 years, we’ve come to realize that they play a major role in brain physiology and pathology and are involved in a number of functions that, in the past, were considered neuron functions. Genomic studies of neurological disorders show that many of the genes that are mutated and change are glial genes. So, big changes occur in these cells, and it appears they have a role in the pathology of alcoholism and other conditions.

I study one particular glial cell type, astrocytes, that we now know are involved in the regulation of neuronal development. When we characterized the proteins released by these cells by proteomics, we identified many extracellular matrix proteins. During brain development, astrocytes release both extracellular matrix components that inhibit neuronal development (i.e. axonal and dendrite extensions) in certain directions and extracellular matrix components that promote neuronal development in other directions in temporary and spatially specific patterns. These components contribute to the formation of the proper network architecture. Later, in order for synaptogenesis to occur, astrocytes modify the factors they release. What we found is that when you treat the astrocytes with alcohol, you have a dysregulation of proteins being released, leading to inhibited neuronal development. Furthermore, when alcohol is removed from the astrocytes after treatment, the dysregulation persists. Astrocyte-mediated dysregulation of neuronal development has been reported also in other neurodevelopment disorders such as Down syndrome, fragile X syndrome, and Rett syndrome. The specific effects are different, but dysregulation of astrocyte function is common to several neurodevelopmental disorders.

For a diagnosis of FAS, growth retardation, neurodevelopmental dysfunction, and specific facial dysmorphic characteristics need to be present. However, even in the absence of these facial characteristics, heavy prenatal alcohol exposure can cause permanent cognitive and behavioral dysfunction. We know that alcohol affects brain development throughout gestation. We also know that binge drinking can be more destructive than lower levels of constant exposure. When alcohol exposure is milder or happens later in pregnancy, some of the physical characteristics associated with FAS may not be present or may disappear with age, making FASD particularly difficult to diagnose. While FAS is an official medical diagnosis, FASD is not. This means people suffering from it aren’t always eligible for government assistance, and yet these individuals may be severely impacted. Many of them have low cognition, extremely poor judgment, a tendency to abuse alcohol or other substances, and sadly, sexual disinhibition, which leads to pregnancies in young women who also drink. And the cycle continues. It’s very sad.

Does your research address treatment or prevention?
I have a program that looks at supplementation of choline during alcohol exposure in the rodent equivalent of  the third trimester of human gestation to see if it improves outcomes as other studies have indicated. I’m looking at the mechanisms by which choline may improve the effects of alcohol on the fetus. We have shown that ethanol affects DNA methylation in astrocytes. In this study, we explore whether epigenetic changes in DNA methylation induced by ethanol in astrocytes can lead to reduced neuronal structural plasticity and behavioral anomalies. Choline can modulate the epigenetic processes of DNA and histone methylation, but also it is a common dietary supplement that is safe to take by pregnant women and infants/children. Therefore, choline represents an ideal potential treatment to prevent and/or ameliorate the effect of excessive alcohol drinking during gestation.

What do you like to do for fun?
Well, work and family take a lot of time. What we have been enjoying is taking small trips around Oregon. We like to cook, and my favorite thing to make, because I like to eat it, is homemade gnocchi. So, we like to hike and we like to eat. My husband wants to try a new restaurant every week because the food in Portland is so fantastic. We’re delighted to be here!