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Upstate researchers examine the brain for studies on addiction, psychiatric diseases and dementia

What do drug addiction, neurodevelopmental disorders and dementia have in common?

All three disorders have origins in the brain, with causes and potential treatment methods that tend to overlap. For instance, they are all caused, at least in part, by a damaged prefrontal cortex, the brain structure that controls our cognition, emotion and memory, and altered neural connections and communications between this and other regions of the brain.

Neuroscientists at Upstate, led by professor Wei-dong Yao, PhD, study the brain and have a variety of collaborative research projects that deal with addiction, psychiatric diseases and dementia.

What they learn about dopamine — a neurotransmitter linked to reward and addiction, and synaptic plasticity — helps in the understanding of schizophrenia and other neuropsychiatric diseases. And, learning about the synaptic loss that leads to frontotemporal dementia may actually reveal new ways of treating this devastating early-onset neurodegenerative disease.

Yao is a professor of psychiatry and behavioral sciences, and neuroscience and physiology who came to Upstate in 2014 after 10 years on the faculty at Harvard Medical School.

Addiction

For more than a decade, Yao has been working on how cocaine impairs the brain by hijacking the dopamine reward circuits. These are the brain’s cortical and limbic structures where dopamine is made and detected that are associated with our ability to feel pleasure.

“Some people are more vulnerable or susceptible to drugs,” he says, explaining that certain mutations on certain genes influence a person’s vulnerability. But that only tells part of the story. Yao’s neuroscience research lab at Upstate is working to tell more.

Using a powerful microscope that allows them to view the junctions between neurons called synapses, and sophisticated electrophysical recording equipment, Yao’s research team explores how neurons communicate in addicted brains – and whether that affects how susceptible a person will be to addiction.

Ultimately, he would like to come up with a way to treat addiction by repairing the synapses and neural circuits in the brains of cocaine addicts.

Neurodevelopmental disorders

Abnormal levels of dopamine have been linked to schizophrenia and other psychiatric disorders.

In Yao’s lab, researchers have provided evidence on how excessive dopamine impairs synaptic plasticity in the prefrontal cortex, which represents a significant step forward in our understanding and potential treatment of schizophrenia and attention deficit hyperactivity disorder, ADHD. They have also studied the medication, clozapine to learn how it may improve cognitive deficits associated with schizophrenia.

In collaboration with colleagues at Mount Sinai School of Medicine, Yao is also studying a group of genetic switches on our DNA, known as epigenetic modifiers, that control synapse and brain development and are linked to schizophrenia, autism and depression.

Dementia

Yao is looking for a way to help people with a type of dementia that affects the frontal and temporal lobes of the brain.

Synapses change over time. This ability is called plasticity. They can become stronger or weaker or disappear, which impacts neural communication, cognitive function and behavior.

Neuroscientists have learned that symptoms of cognitive impairment and dementia arise with synaptic loss. Keeping neurons active and maintaining existing synaptic connections can help alleviate symptoms, Yao says, adding that exercise, including mental exercise such as meditation, can help preserve brain plasticity and prevent the loss of synapses. Exactly how that is achieved is currently unknown.

Yao’s team is working on strengthening and stabilizing synapses by tweaking some proteins within the neurons. Eventually, Yao believes scientists will find a more physiological way to keep neurons healthy and synapses stable. He also hopes to find a way to delay or prevent the death of neurons, through controlling the brain’s natural electric activity, a project he’s working on with a colleague at the University of Massachusetts Medical School.

Caption: Professor Wei-dong Yao, PhD, is leading collaborative studies on the brain that deal with addiction, psychiatric diseases and dementia.

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