Chinese scientists transplant human brain cells to mice, boosting pleasure levels

 

Chinese scientists have found a way to turn human stem cells into dopamine-producing brain cells, transplanting them into mice and helping reduce depressive behaviour and boost pleasure.

When the engineered neuron-like cells were grafted into depression-model mice, they helped lessen symptoms like anxiety and resignation while increasing feelings of enjoyment.

The development has the potential to be employed as a therapy to treat neuropsychiatric disorders by directly targeting and repairing parts of the brain involved in mood regulation.

“This study provides proof-of-concept evidence supporting the use of cell therapy to treat psychiatric disorders by specifically reconstructing dysfunctional neural circuits,” the researchers said in a paper published in the peer-reviewed journal Cell Stem Cell on August 11.

Major depressive disorder ranks among the top contributors to global disease, affecting hundreds of millions of people around the world.

Some experience treatment-resistant depression, which is associated with symptoms like anhedonia, or an inability to experience enjoyment from once pleasurable activities. Anhedonia can persist even after mood symptoms are alleviated.

Dopaminergic neurons are a special type of cell that produce and release dopamine, a neurotransmitter involved in motivation, reward and movement. Depressive patients with anhedonia can exhibit a state of reduced dopamine activity.

Within the midbrain, there are three main subtypes of dopaminergic neurons: A8, A9, and A10. Among these, A10 plays a key role in reward and incentive-based behaviours.


Dysfunction of the A10 neuron system has been linked to psychiatric disorders, including depression, schizophrenia and drug addiction. This has made A10 neurons a target cell for the treatment of these disorders.

Human pluripotent stem cells, which can differentiate into all cell types, have been used to generate dopaminergic neurons, including A9, though the team said that efficient generation of A10 neurons had previously been “elusive”.

The team from the Chinese Academy of Sciences at Fudan University and stem cell therapy company UniXell Biotechnology developed a method to generate A10-like cells by giving human stem cells a special mix of chemicals at a specific stage of differentiation.

The resulting engineered neurons exhibited the same molecular and electrical properties as A10 neurons.

When the engineered neurons were transplanted into depression-model mice generated through exposure to chronic stress – exhibiting symptoms like resignation and loss of pleasure – they led to “significant antidepressant-like behaviours”.

This included relieving anhedonia and behavioural despair, a state in which animals stop attempting to escape from stressful situations, such as the threat of drowning, and become immobile.

The team found that the transplanted neurons were able to effectively integrate into neural circuits, including receiving signals from surrounding neurons, “demonstrating their potential for repairing dopamine-related pathways”.


The specificity of the neural cell therapy could offer a “significant advantage” over broad pharmaceutical drugs by providing fewer off-target side effects, according to the researchers.

“This study provides strong proof of concept for [A10-neuron-based] therapy in the clinical treatment of major depression and extends the potential applications of cell-based therapy for psychiatric disorders,” they said.

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