Of Mice and Men and Girls and Autism

Khaoula Ben

With Trinity College currently celebrating 25 years of Neuroscience, there is no better time for us to have a neuroscience-focused school president. President Berger-Sweeney’s talk last Thursday revolved around the past 15 years of her research, during which she studied autism spectrum disorders in mice. When she first began her studies, rats were the more commonly used models, but she switched her focus to better understand the correlation of mice and human genomes. In order to be able to model a human disorder in an animal like a mouse one must tackle some if not all of the following characteristics and ensure that there is overlap: symptoms, genetics, chemical changes, brain anatomy, among others. Of course, mice and humans are anatomically and physiologically difference. For example, while mice don’t speak in the way that humans do, they make ultrasonic vocalizations, which make them similar enough.

The next question that come up after finding a suitable model is finding a way to properly model the disease in question. President Berger-Sweeney studied pervasive developmental disorders, which interrupt normal neural in childhood and require early treatment, particularly an autism spectrum disorder known as Rett syndrome. Autism, by definition, is a genetically and epigenetically influenced disorder that reduces social interaction, communication, and joint attention. Furthermore, in the United States, 1in 110 children are affected, it with four times as many being male. (Schavietz and Berger-Sweeney, 2012). Rett syndrome, more specifically, is a regressively developmental disorder, which mostly affects 1/2000 live births, particularly girls, since boys rarely survive to birth (Katz et al., 2012). The most common symptoms are difficulty with communication and hand wringing/flapping. These girls appear healthy at birth but development slows down at 6-18 months, followed by rapid regression in years 1 to 3, when they exhibit stunted head and physical growth, seizures, and more autistic characteristics. Years 5 to 10 are a period of pseudo-stabilization, while adulthood is tinged with a regression into scoliosis. Few girls survive past age 30, a worrisome trend.

Rett syndrome’s “cause” has been attributed to a transcriptional repressor, methyl-CpG-binding protein 2 (Mecp2), which usually blocks the transmission of the gene (Katz et al., 2012). Loss of this repressor means a loss of control over the gene that causes the condition. In 95% of Rett syndrome cases, this loss is caused by a spontaneous mutation on an X chromosome. Unfortunately, at this point in time, Rett syndrome is currently not entirely treatable. However, some nutritional supplements and drugs like choline, Acetyl-L-Carnitine (ACL) and Galantamine butyl-carbamite have allowed for some progression and improvements (Katz et al., 2012). The next step for this research would be to continue experimentation in hopes of finding the ultimate cure.

Unfortunately, with autism affecting 1 girl for every 4 boys (Schavietz and Berger-Sweeney, 2012) and more specifically, Rett Syndrome affecting only 1 in 10,000 girls, (Katz et al., 2012), they are often misdiagnosed, leading to preventable progression (Willingham, 2015). Not to mention, of course, the stigma associated with neurological conditions is amplified in autism with its extremely visible symptoms, worsened by the fact that Rett syndrome affects young girls who are thus bullied and often turn to eating disorders and depression (Willingham, 2015). Talks like the one President Berger-Sweeney presented are important in educating the public and keeping people aware of conditions which plague such helpless children. I know that I, for one, had absolutely no knowledge of Rett Syndrome’s existence before her talk.

President Berger-Sweeney’s talk

Jonah Meltzer

The 15+ years of research presented by President Berger-Sweeney on her work with Rett’s syndrome was both informative and offered insight into current areas of research. During her talk the President focused on the general information about the disease, what it is and how it affects people, as well as more specific information about what the results with a mouse model reported. The disease is classified as an Autism Spectrum Disorder (ASD). It affects young children, mostly girls, and manifests itself at around 12-18 months. The mutations occur in the MeCP2 gene, a protein that regulates the transcription of genes. The disorder differentiates itself from other neurodegenerative diseases due to what is known as the “plateau stage”, in which the regression of skills halts and there is no further regression. Later in life however, the affected individuals may re-enter a stage of motor decline later in life and develop parkinsonism-like symptoms. Due to this regression the occurs later in life the average age of a person affected with Rett’s syndrome is around 30 years-old.

President Berger-Sweeney’s talk was a great opportunity to get to know her as a researcher and for the rest of the Trinity community to see her as a neuroscientist. Moreover, it was a nice opportunity to learn about a disorder that is not often mentioned in conversation with the more notable Autism Spectrum Disorders. Ultimately, I was able to learn more about our wildly over-accomplished President, her research related passions, and what it truly means to love the work and research that you do.

Of Mice and Men and Girls and Autism – A lecture by President Berger-Sweeney

Chloe White


In her lecture entitled Of Mice and Men and Girls and Autism, President and
Neuroscience Researcher Joanne Berger-Sweeney spoke of her work looking at neurological
diseases in mice. When using a mouse as a model for a human disorder, she looks for four major
similarities: a mouse that models the symptoms, genetics, chemical changes and brain anatomy
of the human. Specifically, President Berger-Sweeney has studied Rett Syndrome, an autism
spectrum disorder that affects mostly females. Rett Syndrome, a regressive developmental
disorder, causes difficulties in communication and repeated hand-flapping motions. Often, the
Rett Syndrome girls only live until 30 years of age or so. One of the hardest parts about this
disorder is that until approximately 6-18 months, the girls seem neuro-typical until they start to
regress. During a period of rapid regression which occurs between 1-3 years, the girls present as
autistic, and develop habits such as the hand flapping motion. In a pseudo-stabilization period,
the autistic symptoms regress and respiratory problems begin. It’s these respiratory problems that
only allow the girls to live until 30 years.
Although I knew about this syndrome before her lecture, there was a specific detail that
President Berger-Sweeney mentioned that I was unaware of. Rett Syndrome is a syndrome where
the regulation of genes has been lost. This occurs when there’s a problem with a transcriptional
repressor known as Mecp2. Normally, Mecp2 blocks gene transcription. However in this
syndrome, it itself is inhibited so that it can no longer inhibit gene transcription. This causes the
genes to not be regulated enough. Mecp2 is located on the x-chromosome, and is associated with
95% of Rett Syndrome cases. Although this is a very high percentage, it was not enough for
President Berger-Sweeney, so her research continues.
One experiment that President Berger-Sweeney has run on her mice is called the Social
Approach experiment. In this experiment, she monitored how much time mice that modeled a
Rett syndrome like disease chose to spend alone verse with other mice. She hypothesized that
they would be more eager to spend time alone. However, the data she collected did not support
this. Instead, she found that mice spent most of their time with the other mouse (which was in a
cage). When she went to talk to the parents of girls with Rett Syndrome, they stated that the girls
can actually be very sociable. This portrays one of the most important parts about doing research:
you have to take the data as it comes. Although this data initially did not support President
Berger-Sweeney’s research, she could not alter it in any way to support her study. Instead, she
went back to her research and has been conducting more tests in order to find a cure for this

Joanne Berger-Sweeney’s Research Provides an Exemplary Model for Undergraduates at Trinity College


Nathaniel Thiemann


Leading by example sets a precedent for what is expected, and promotes solidarity by showing that even the person in charge is conducting themselves by that standard. However, in today’s world it is all too common for a person in a position of leadership to take a “do as I say, not as I do” mentality. While this mentality may make sense in some unique instances, it is often better for leaders to lead by example. A leader who sets and meets their own standards effectively establishes what is expected, and demonstrates that the person with the greatest responsibility is capable of meeting these expectations. Joanne Berger-Sweeney’s talk last week at the Trinity College Common Hour exemplified what it means to be a person who leads by example.

One of the goals of any academic institution is to further people’s understanding of various subjects. In her talk last week, Berger-Sweeney showed how she expanded our understanding of autism before she ever stepped into her current administrative role. Berger-Sweeney’s contribution was to the scientific community’s understanding of Rett syndrome, a regressive form of autism spectrum disorder, which only affects girls. When listening to Berger-Sweeney talk, her passion for the research and its implications was unmistakable. The president of Trinity College’s passion is one such example of a quality that she is looking for out of the college’s community, that she clearly embodies herself.

One other quality which Berger-Sweeney exemplified during her brief talk was logic, which she exemplified in several ways. From her informed selection of what animal model to use, to her attempts to treat Rett syndrome Berger-Sweeney always showcased critical thinking of a holistic nature. Young scientists at the school can learn a lot from her implementation of the scientific method. She effectively determined a problem, researched it, experimented, and then tested possible solutions.

More examples of good leadership can be found, buried with in Berger-Sweeney’s talk and her history. She embedded advice for her young listeners into her talk, turned down cash incentives that introduced bias to her research, and demonstrated dedication to a task. While her work may be just a small addition to our understanding of autism, her exemplary behavior is a huge addition to her status as a leader.

President Berger-Sweeney

Beth Foley

Since becoming president of Trinity College last fall, I’ve heard President Berger-Sweeney speak on many occasions. I was fortunate enough to witness her eloquent speech at her inauguration, as well as at the most recent Trinity College graduation. I’ve overheard her speaking to classmates, and I’ve even had the pleasure of exchanging words with her while out on a morning walk with her dog. However, after hearing President Berger Sweeney’s scientific talk, it was very clear to me that she is most in her element when talking about her research. In a clear and passionate manner, President Berger-Sweeney shared details with those of us present at her opening talk for the 25 years of neuroscience program regarding her work with pervasive neurological disorder, specifically Rett syndrome.

Although it was evident that President Berger-Sweeney wanted her presentation to be comprehensible to all students, I found that my fellow neuroscience majors and I were particularly well equipped to understand the many facets of her research. In addition, as a student involved with behavior neuroscience research lab with autistic mouse models, I feel I had a unique appreciation for President Berger-Sweeney’s work.

To begin, President Berger-Sweeney spoke briefly about her choice to work with mouse models instead of rats due to the amount of information know about the mouse genome. President Berger-Sweeney then delved deeper into her interest with Rett Syndrome, a regressive developmental disorder that is associated with mutations in the gene encoding MeCP2, a transcriptional repressor. President Berger-Sweeney played a short video of a young female named Esme, who represented one of the many girls with Rett syndrome. Esme had difficult with commination, characteristic had flapping gestures, irregular breathing, and was predicted to develop more of the typical complications such as loss of mobility, seizures, and scoliosis.

It was then that President Berger-Sweeney began to talk more thoroughly about the many ways she sought to find an effective treatment for Rett Syndrome. An integral finding for her research team was the role of the cholinergic system and it’s relation to reducing the negative effectives of MeCP2 mutation. Her first experiments involved the delivery of choline into her pregnant mouse models via drinking water. Her research team then assessed the development and behavior of the offspring of the pregnant models. Although such results suggested that the choline helped with increased motor coordination, neuronal health, and brain volume, there was no significant indication that cognitive development of the models were improved. Such results lead to her next experiment in which a precursor of acetylcholine, ALC, was injected into the mice. After examining cells in the dendate gyrus, it was found that ALC was in fact improving the neuronal morphology in her mouse models by increasing dendritic branching and overall neuron density. Essentially, the general health, motor function, and cognitive development were improved just as her team had hoped, but only up to post-natal day 30. At this point, a general decline of such functions was found.

After discussing some other directions for her research, as she still plans of working to find a treatment for Rett Syndrome, President Berger-Sweeney took time to acknowledge all the students that played a role in her research journey. She specifically mentioned one of her female students who struggled after graduating from Tufts with balancing her passion for scientific research and her family life. President Berger-Sweeney mention to her audience, most directly to the females in the room, that a career in science is not an easy feat, but that with genuine intellectual curiosity, dedication, and love of your work it is possible to successfully balance it all.

Ultimately, I left President Berger Sweeney’s talk with a clear picture of her passion for neuroscience, for research, and for improving the quality of life for individuals with Rhett’s syndrome. It is rare that scientific talk is both intellectually stimulating and poignant, yet I feel President Berger Sweeney hit this sweet spot. Overall, I felt the presentation “Of Mice and Men and Girls and Autism: Insights from 15 years of studying the neurobiology of mouse models of autism spectrum disorders,” was a perfect way to kick start 25 Years of Neuroscience at Trinity College.

Of Mice and Men and Girls and Autism

Elizabeth DiRico

To initiate Trinity College’s celebratory Twenty-Five years of Neuroscience series president Joanne Berger-Sweeney discussed the extensive research that she has conducted on Rett syndrome over the past 15 years. A pervasive neurodevelopment disorder categorized on the autism spectrum that plagues young girls. Symptoms of Rett syndrome typically appear around six months of age, including purposeless arm motions, difficulty with speech and slow cognitive development.

The cause of this disorder is a mutation to the MECP2 gene, a repressible gene that is responsible for producing and regulating MECP2 protein production as well as additional protein production. A random mutation in the MECP2 gene results in inappropriate regulation of protein synthesis, the operon has no ability to turn off DNA transcription and excessive protein is produced. There are significant repercussions for this single gene mutation because MECP2 is an essential protein in neurological development. The bodies inability to regulate gene production impairs the nerve cells and resonates in the form of debilitating neurological symptoms. Due to the genes location on the X chromosome, Rett syndrome is exclusively observed in girls. Girls second X chromosome is essential for compensating for the mutation, where as males do not have the second set of genes and are not able to survive such a crippling mutation.

President Berger-Sweeney first set out to investigate the effect of acetylcholine on MECP2 function. A major hurdle she encountered in her early experimental design was choosing a test subject that would closely mirror human symptoms. Her decision to use mice as a test models opposed to rats based on a more extensively sequenced genetic code, set her ahead of her time. The MECP2 mutant mice produced many symptoms of Rett patients right down to the stereotypical hand grabbing customary to young girls with Rett syndrome.

The effect of acetylcholine was investigated by feeding choline supplements to pregnant mice. The results demonstrated an overall improvement including increased brain volume, motor coordination, growth factors and neuronal health. In her published research, her finding showed that Choline supplements played a role in regulating DNA and histone methylation. She aimed to take this approach a step further my implementing chromatin remodeling drugs in place of supplements to better control DNA and histone methylation. Following the tremendously impressive results of the previous studies, President Berger-Sweeney began experimenting with Acetyl-L-Carnitine a drug she described as “choline on steroids”. Instead of a supplement, this drug was injected a does per day for thirty-six days. The results pertained form these experiments were even more impressive than the previous experiments. The overall health of mutant mice brain improved continuously up until day thirty, dendrites were examined and found to be longer and more extensively branched than before. The take away message was that the key to reversing the effects of Rett syndrome is early intervention.

Although President Berger-Sweeny is at the forefront in Rett syndrome research and has yielded impressive results, in terms of improving Rett syndrome, she will not be satisfied until she finds a cure. She spoke of feeling both an obligation and a connection to the girls who suffer from Rett syndrome. For her future research she hopes to explore the carbon metabolic cycle and believes that this process may play a role in the underlying mechanism of many developmental disorders, including Rett syndrome. Although President Berger-Sweeny has taken off her lab coat in order to step in to an administrative role, she fully intends to return to her research in some capacity.

President Berger-Sweeney & Rett Syndrome

Tommy Hum-Hyder

In her talk entitled, Of Mice and Men and Girls and Autism, President Berger-Sweeney reviewed her years of research looking at the relationship of the MeCP2 transcriptional regulatory protein on a mouse model of Rett Syndrome (Katz et al., 2012). The crux of her research was focused on the 1 in 10,000 females, who are born with this regressive developmental disorder. For the first 6-18 months post-natal, the child appears to develop normally; subsequently, muscle begins to atrophy, difficulty crawling or walking, as well as Autism Spectrum Disorder (ASD) type symptoms, such as reduced eye contact. (NINDS, 2015).

Prior to President Berger-Sweeney’s research, scientists believed that the cognitive and behavioral abnormalities associated with Rett Syndrome were due to deficits in the cholinergic system, which they believed was due to abnormalities in the MeCP2 protein, a transcriptional repressor protein. Berger-Sweeney and team decided to proceed with a mouse model despite many colleagues in other research fields using rat models. President Berger-Sweeney spoke of the importance of a good animal model and of the first questions that her research group asked, which included whether to model symptoms, genetics, neurochemical changes, or neuroanatomical changes. The group decided to proceed with a mouse model with MeCP2 gene knockouts.

After many years of research, the group found that the male mice with the gene knockout made to replicate Rett Syndrome experienced an increased in social behavior, which, at first, seemed to contradict typical Rett Syndrome symptoms. However, a literature review suggested that it is possible for Rett Syndrome human females to have increased social behavior, suggesting that the mouse model could be a good measure. The group then decided to look at ways in which they could take this effective genetic mouse model and try to improve symptoms. They began by using choline, a precursor molecule of the neurotransmitter acetylcholine. At muscle junctions, acetylcholine facilitates muscle contractions. Research has also suggested that it may be involved with awareness and attention, which could address cognitive Rett Syndrome symptoms. After positive results, the group decided to use an acetylated version of the l-carnitine molecule called acetyl-l-carnitine, which they gave to mice as a nutritional supplement. They then improved results relative to the choline treatments, but results also showed that the improvement only lasted until 30 days postnatal. This would lead to inconclusive results relevant to the treatment of Rett Syndrome in humans; however, due to few researchers interested in Rett Syndrome, any progress towards the eventual amelioration of symptoms can be considered a great advance in the study of females with Rett Syndrome.

From the Tripod-Andrew Hatch

On Thursday, Sept. 17, President Joanne Berger-Sweeney gave a lecture beginning a yearlong celebration of neuroscience within the Trinity community. Overseeing the festivities was neuroscience department chair Prof. Sarah Raskin. Students, faculty, and the Hartford community packed the Washington room last Thursday to listen to the president discuss her years of research on Rett Syndrome, a form of autism exclusive to girls.

The president’s lecture was segmented in two parts: The first, a general overview of Rett Syndrome, and the second being an in-depth accounting of the known genetic causes and possible treatments. Much of her research has been focused on trying to establish possible treatments for the condition as well as to recreate and test the work of others to help assess the validity of their research.

Throughout her talk, the president shared many personal anecdotes and continuously stressed persistence. She realated her experience of trying to gain the attention of a famed neuroscience researcher, which took her many phone calls. The President also playfully recounted an experience where her lab rats were sent from a colleague’s lab in Boston to her lab at Wellesley College via taxicab. On a more serious note, her research has revealed several causes of Rett Syndrome and identified several treatments. In her research, Dr. Berger-Sweeny has tested the effectiveness of her colleague’s treatments, though in several regrettable cases she found them to be ineffective. Fortunately, her joint research with a fellow colleague has produced and patented a compound they hope might be a viable treatment.

President Berger-Sweeney concluded her talk with some advice to budding young scientists; persist, ask questions, and ensure you have a strong support group. The president thanked her family for their tireless support of her as well as thanking her many colleagues in the scientific community, as well as her many undergraduate research assistants. President Berger-Sweeney’s lecture set the stage for a year which will feature a divers array of neuroscience related events, ranging from art and music, to scientific symposiums and guest lectures.

Of Mice and Men and Girls with Autism: Presentation by President Berger-Sweeney

Amina Kureshi


On September 17th, our own President Berger-Sweeney gave a talk on the neuroscience research she has published. Rett Syndrome, which is on the Autism Spectrum Disorder, is a severe developmental disease which affects boys and girls alike. Rett syndrome is characterized by short term overconnectivity and long term underconnectivity of neurons. Unfortunately, boys with Rett Syndrome do not survive birth, so the disease is known to affect girls. It causes motor dysfunction as well as respiratory issues, which leads to a low survival rate after the age of thirty.


There is no known cause of Rett syndrome, so how do we give mice Rett syndrome so that we may study it further?  It was found that the Mecp2 gene is downregulated in about 95% of cases of Rett syndrome. Therefore, eliminating the Mecp2 gene in mice will be an electrical, biochemical, genetic, and neuroanatomical analog to the human condition, as genes regulate development from conception. So these mice which have the Mecp2 gene eliminated then have to be tested to determine how closely they model the disease in humans. Therefore, testing was done to determine the sociability, motor skills, respiratory ability, cognitive function, ect.. Once these mice were tested, and determined to be a viable analog to Rett syndrome, they were used to study treatments for Rett syndrome.


The Mecp2 protein is used to regulate transcription of genes by binding to the promoter region of the gene and recruiting other proteins to block transcription of the respective gene. Therefore, when the Mecp2 gene is not producing the Mecp2 protein, the gene that it normally blocks is upregulated. It is theorized that this is the cause of Rett syndrome.


Acetylcholine, which is a neurotransmitter used to communicate a signal from a neuron to a muscle can be upregulated by increasing its precursor, choline. Therefore, the research conducted in Prof. Berger-Sweeney’s lab used choline as a nutritional supplement in pregnant Mecp2 mice to determine its effectiveness in preventing the onset of symptoms, particularly the cognitive symptoms. It was found that the treatment did improve symptoms, but not for the entire lifespan of the mice born having had the nutritional supplement. New avenues for research are looking into the C1 metabolism pathway to improve acetylcholine function.


The president’s talk was well thought-out and proved her scientific “chops” to us undergraduate students. Indeed, she schooled us with questions about the byproducts of the Kreb’s cycle and other biochemical mechanisms. My impression is that President Berger-Sweeney would make a good Neuroscience professor not only in lecture, but also in laboratory research. If only she had a research lab at Trinity for us students to benefit from. Perhaps the most memorable part of her talk was a shared story of another fellow female neuroscientist who was her mentee. This woman wanted to start a family and in order to be a full time mom, she was seriously considering leaving the sciences as a profession. President Berger-Sweeney, in response to hearing this, told her to work in her lab, and eventually she rose the ranks to hold a prestigious position in the sciences. This message is especially important for the female science majors, myself included, as it gently reminds us and inspires us to live a full and complete life without having to sacrifice home life for career or vice-versa.

BIAC Internship: Week 3

First off, an announcement: I found a food truck!  Julie was a little nervous, but it all worked out.

The thing I am seeing less success with is sponsorships.  I’m not sure if it has something to do with seeing my name instead of Christine’s, or if I am simply going about it in the wrong way (though I do copy Julie’s format each time I send out an email soliciting a sponsorship from a specific company).  It also could be that it’s simply a tougher task.  On the bright side, the new development director starts on October 1st, so communicating with potential sponsors with won’t be part of my job for much longer.

It feels as though I am making significant progress.  I don’t have the prior experience to judge where I am in the planning process as compared to where I should be, but it seems like things are moving along well.

It’s also easy to lose myself in the tasks and forget why I do this work.  At CASO today, someone new came in.   She has been concussed for almost five years.  As she was telling me about her struggles (and signing up for Team Trinity), I was reminded of the people I’m working for.  As I heal, it’s easy to lose touch with how difficult it used to be to even have a conversation with someone.  My meeting with this person helped put me back in touch with the struggles of a survivor.  I hope this humble reminder stays with me for awhile.