Two MIT neuroscientists have received donations from the G. Harold Foundation and Leila Y. Mathers to screen for genes that may cause brain cells to be resistant to Parkinson’s disease and to map how gene expression changes in the brain in response to substance abuse.
Myriam Heiman, Associate Professor in the Department of Brain and Cognitive Sciences and a founding member of the Picower Institute of Learning and Memory and the MIT and Harvard Broad Institute, and Alan Jasanoff, who is also Professor of Biological, Brain and Brain Engineering Cognitive Sciences, Nuclear Science and Engineering and Associate Researcher at the McGovern Institute for Brain Research received three-year awards that formally began on January 1, 2021.
Jasanoff, who also directs the MIT Neurobiologic Engineering Center, is known for developing sensors that monitor molecular signals of neural activity in the living brain, in real time, through noninvasive MRI brain scanning. One of the MRI-detector sensors he developed is dopamine, a neuromodulator that is fundamental in learning what behaviors and contexts lead to reward.
Artificially addictive drugs drive dopamine release, thus taking over the brain’s reward prediction system. Studies have shown that dopamine and abuse drugs activate gene transcription in specific brain regions and that this gene expression alters how animals are exposed to drugs again.
Despite the important effects of these neuroplastic changes for the addiction process, in which drug-seeking behavior is forced, effective tools are not available to measure gene expression throughout the brain in real time.
With the new Mathers funding, Jasanoff is developing new MRI-detection sensors for gene expression. With these advanced tools, Jasanoff recommends making an activity atlas of how the brain reacts to abusive drugs, both when they first appear and over regular doses that are similar to experiences of individuals with drugs.
Our studies link drug-induced brain activity to long-term changes that reshape the brain into addiction. We hope that these studies will recommend biomarkers or new treatments. “
Alan Jasanoff, Professor of Biological Engineering, Brain and Cognitive Sciences, Nuclear Science and Engineering and Associate Researcher, McGovern Institute for Brain Research
Parkinson’s Project
Dopamine-producing neurons in a brain area called the substantia nigra are known to be particularly at risk of dying from Parkinson’s disease, leading to the severe motor problems suffered when the deficiency occurs. harmful, inevitable neurodegenerative prescription.
The field has little information about what puts particular cells at such high risk, or what molecular mechanisms might help them fight the disease.
In her research on Huntington’s disease, another unstable neurodegenerative disorder in which a particular neuron population in the striatum is particularly vulnerable, Heiman has been able to use an innovative approach that started her laboratory. to find genes that promote neuron survival, highlighting potential new drug targets. .
This method involves making a neutral screen in which her lab breaks down each of the 22,000 genes expressed in the mouse brain one after the other. one in neurons in disease model mice and healthy controls. This method allows her to find out which genes, when needed, contribute to neuron death in disease and therefore which genes are specifically needed for survival. .
The results of these genes can be evaluated as drug targets. With the new Mathers award, Heiman plans to implement the method to study Parkinson’s disease.
“There is currently no molecular explanation for the loss of brain cells seen in Parkinson’s disease or a cure for this devastating disease,” Heiman said. “This award will allow us to make genome-wide, nonsensical genetic shadows in the brain models of mouse models of Parkinson’s disease, detecting genes that allow brain cells to survive from the effects of Parkinson’s-related cells . I am extremely grateful for this generous support and recognition of our work from the Mathers Foundation, and we hope that our study will contribute to new therapeutic targets for the treatment and even prevention of Parkinson’s disease. “