Professor wins prestigious prize for groundbreaking discovery in use of ketamine

Source:Global Times Published: 2019/10/17 19:23:40

Photo: VCG

Hu Hailan, a professor at Zhejiang University School of Medicine, won the 12th International Brain Research Organization (IBRO)-Kemali International Prize for Research in the field of Basic and Clinical Neurosciences in July 15 for further explaining the pathogenesis of depression.

This is the first time that the IBRO-Kemali Prize has been awarded to a scientist outside of Europe and North America since it was established in 1998, according to the website of IBRO.

The award ceremony will be held on July 11 to 14, 2020, at a forum of the Federation of European Neuroscience Societies. In her speech at the ceremony, pecking order theory and ketamine will be the keywords, which were also the keywords of Hu's research in recent years, reported Qianjiang Evening News.

Fast-acting antidepressant

According to the latest statistics of the World Health Organization, a total of 350 million people in the world suffer from depression, and as many as 1 million patients with depression commit suicide every year.

Hu and her team discovered the connection between bursting neurons and depression. Renowned international science journal Nature released two research articles in the same issue on February 15, 2018 about research into depression carried out by Hu and her team.

Hu's research further explains the pathogenesis of depression through explaining the working mechanism of ketamine, a fast-acting antidepressant, and provides more molecular targets for the development of new antidepressants.

"It takes traditional antidepressants weeks and months to improve emotions, with only a 30 percent recovery rate," Hu said, according to the website of Zhejiang University. "It reminds us that existing antidepressants might work indirectly and our understanding of depression still hasn't tackled the core of the disease," Hu added.

A file photo of Hu Hailan Photo: Screenshot of Zhejiang University website

In recent years, ketamine, an anesthetic, has brought new light to mental disease treatment as scientists found that a small dose of ketamine can have an anti-depression effect in as little as one hour, and works in treatment-resistant depression patients, who make up 70 percent of depression patients.

With its fast-acting anti-depression mechanism, ketamine has been hailed as the most remarkable discovery in mental disease treatment in the past 50 years.

However, questions such as how ketamine works on which brain area and why it works so quickly are key for people to understand and cure depression.

Discovering the causes

Hu and her team first found that a neuron burst firing model is a sufficient condition for depression, and the working mechanism of ketamine stops neuron bursting in the lateral habenular nucleus (LHb).

LHb appears as a small core under the hippocampus in the brain, which is believed to conduct most negative emotions such as fear, nervousness, and anxiety. It "fights against" monoamine neurotransmitters in the reward center of the brain to control people's emotions.

In normal conditions, neurons transfer information to downstream nerve cells through single neuron firing. If the firing model becomes high-frequency bursting, depression occurs. 

"Normal mice show single neuron firing, while depressed ones show more bursting, in the same way a shotgun becomes a machine gun, sending information in a more effective manner with intensive bullets," Hu said, according to the website of Zhejiang University. 

"These amplified signals strengthen the inhibition of LHb to reward centers, which makes mice unhappy and depressed," added Hu.

Hu and her team conducted the famous forced swimming test, in which healthy mice struggle to stay alive, while depressed ones showed despair and stayed still.

In another sucrose preference test, depressed mice showed no preference for sugar water, indicating anhedonia.

Hu's team found that neurons of LHb in depressed mice have more frequent burst firing. At the same time, normal mice showed various symptoms of depression after their LHb neurons were induced to burst firing by using optogenetics.

After injecting ketamine into the depressed mice's LHb area, their depression symptoms were relieved, including their behavioral despair and anhedonia. 

Hu's experiment is the first time that depression was triggered through changing the firing model of a certain brain area. Her research also found the fast working mechanism of ketamine in treating depression.

Hu and her team found that LHb neuron's burst firing model relies on N-methyl-D-aspartate receptor, or DMNAR, which is the most important excitatory transmitter of brain, and ketamine stops bursting in the LHb area, which makes depressed patients regain the ability to sense happiness.

"The research explains the neural mechanism of how ketamine works so fast in anti-depression. It can stop firing in LHb, relieve the over inhibition imposed on reward centers, and eventually improve depression in a rapid manner," Hu said.

In the other article Hu published in Nature, she found another molecular target to treat depression quickly, which was potassium channel Kir4.1 in glial cells.

Hu found that a high expression of potassium channel Kir4.1 in glial cells triggers bursting. "Although there is still a long way to go for medicinal development, we have seen the light and taken the first step," Hu said.

In the IBRO website, the prize-giving committee spoke highly of Hu's discovery. "In recognition of her impressive work on the fundamental neurobiological mechanisms of emotional and affective behaviors based on very advanced, state-of-the-art methodologies, which she contributed to develop. Overall, she has an outstanding productivity and a well-established, high profile in systems neuroscience, a rapidly expanding and very competitive field."

Global Times
Newspaper headline: Unlocking secrets of depression


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