How does the brain work, and what happens when it doesn’t?

Going back to basics to learn about how the brain works could help guide better treatments for diseases

 

Every second of the day, your brain is fizzing with activity. Your neurons send signals to each other across a tiny gap between them, in turn spreading electrical messages across vast networks to make your brain do what it does.

If that signalling process goes awry, for whatever reason, it can lead to problems, including brain disorders or diseases.

But how much do we really understand about how the brain works and what goes wrong in disease? Not much, according to Nobel Laureate Prof Thomas Südhof, who spoke recently at Dublin City University(DCU) about the importance of research into brain basics.

“We don’t really know how the brain works, and what happens when it doesn’t work,” he says.

It’s not all doom and gloom, though: technological advances are offering us new insights into brain function and disease, according to Südhof, who shared the Nobel Prize for physiology or medicine in 2013 for his work on understanding how brain cells communicate.

Genetic discoveries are changing perspectives, particularly in neuropsychiatric diseases, he notes. “Many mutations, maybe most, that predispose to autism and schizophrenia are mutations that happen new; these are not inherited.”

Meanwhile, Südhof’s own research has pinpointed key events and machinery involved in brain cell communication, and it turns out that some of those cellular players are altered in brain disease.

But this is just the start. Now we need to understand what those changes mean, he notes.

“I think there is a true opportunity to go from the gene mutations to the functional changes to therapeutic intervention. This opportunity, however, depends on understanding what the gene mutations do.”

Without such understanding, we are “guessing” when it comes to identifying therapies, he says.

“We need to focus on understanding the disease before we can focus on developing drugs. If we don’t actually know what we should make drugs against, we can’t make them; the understanding of the disease has to be a priority.”

Gut feeling

Südhof’s talk coincided with the ninth Neuroscience Ireland conference, chaired by Prof Oliver Dolly at DCU, where researchers spoke about their research into brain basics. Some even went beyond the brain, as in the case of Prof John Cryan, of University College Cork, who studies how the bacteria living in our guts (our gut microbiome) could influence brain function.

Cryan agrees that fundamental research is key to developing new strategies for tackling brain diseases and disorders. “We are still in the early days of finding out how the brain works, especially in the context of the neural basis of neurodegenerative and psychiatric brain diseases,” he says.

“In my own research we are focused on how the gut microbiome can signal to the brain. This is a complete paradigm shift in neuroscience and requires a lot more basic research to tease apart the complex mechanisms at play.

“It is gaining a lot more attention in basic neuroscience circles and is a really exciting field [that] may lead to innovative strategies for treating stress-related neuropsychiatric disorders.”

Addiction basics

Unravelling the basics of addiction could also point to new ways to intervene, notes Irish neuroscientist Prof Paul Kenny, Ward-Coleman professor and chairman at the Icahn School of Medicine at Mount Sinai, who spoke at the DCU conference.

His research on addiction and brain reward pathways is finding that being less sensitive to the noxious effects of addictive drugs could play a substantial role in vulnerability to addiction, and he believes such fundamental insights can help lead the way to better treatments.

“The brain is a remarkably complex organ that processes and stores information and guides behavioural output in ways we are far from understanding, and deficiencies in these complex processes are responsible for neuropsychiatric disorders,” he says. “Without understanding better how the brain works, it is unlikely we will have much success in designing effective medications to treat such disorders.”

Scientific race

Südhof likens the process of carrying out the scientific research as running a race, but you don’t know how long that race is.

“We don’t understand any of these diseases but any of the experiments that people are doing could get us an understanding,” he says. “You don’t know if you are running 100 metres or a marathon: you just run, and you hope it is 100 metres.”

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