Wednesday, June 24, 2015

Findings of the relationship between depression and memory in mice model

Recently, a potentially innovative article was published in Nature, a world famous academic journal. The authors claim that activating cells in hippocampus externally could improve the mood in the mouse. This result can contribute greatly to the research of depressive disorders.

Nature: Activating positive memory engrams suppresses depression-like behaviour

The author, Steve Ramirez, belongs to RIKEN-MIT Center for Neural Circuit Genetics. The team administrator is Susumu Tonegawa, a Japanese Nobel Prize winner biologist.

The researchers used a traditional mouse model of depression. Mice given stressor chronically become reluctant to avoid negative stimuli. This status has been considered to represent a depressive state in human. They focus the relationship between depression-like behavior and activity of memory cells. By an experiment, it was proven that some particular cells in hippocampus, considered to be a storage of memory, which had been identified to be activated in a previous trial of enjoyable behavior, were not activated in immobilized state.


Moreover, they succeeded to reactivate such cells located in the dentate gyrus of hippocampus externally with an optogenetic method. It led the mice to revive the action to avoid negative stimuli again.

They also identified glutamatergic activity in the hippocampus–amygdala–nucleus-accumbens pathway as a candidate circuit supporting the acute rescue. It is consistent with the fact that depression brings dysfunction of the emotion and motivation.

The relationship between depression and the memory has been broadly discussed. Recently, a result of research in which an electronic shock could delete traumatic memory was reported. It is well known that a traumatic experience can cause depression. In contrast, we cannot remember delightful memories as so in the depressive state.

My past entry: Trauma deleting therapy with electric shock

To be honest, I do not believe that this model mouse completely represents depression in human. This method is broadly adopted in the animal research to develop antidepressant drugs. As animal cannot talk, we have to estimate depressive state with an observation of their behavior. However, there are patients suffering from depression caused without any overt stress. Some of them hardly respond to medication. I guess such patients have another etiology than that studied with the mouse model.

In this study, the targeted cells were modified with optogenetics so that they can be activated externally in advance. Therefore, it is unlikely that this solution can be directly utilized to human. Nonetheless, their achievement gave a strong evidence about the functional relationship in the brain during depressive state.

I am not familiar with the optogenetic theory. But if you can cause a revelation of genes likely to respond to a particular stimulus in the brain cell, it will apply to enormous utility, from the elimination of cancer cells in the brain to the enhancement of cognitive function. It looks fantastic.

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