04/07/2021 at 1:53 PM CEST
A new study developed by scientists at the University of Wisconsin-Madison sheds light on the biochemical basis that allows the emergence of bipolar disorder. These are alterations of a particular protein called Akt, which generate the changes in the brain that characterize this pathology.
According to a statement, the finding could be an important advance in identifying and treating cognitive deficits related to bipolar disorder that are often underestimated, such as memory loss, contributing to a greater understanding of how the brain’s biochemistry affects health and disease.
Bipolar disorder causes drastic changes in mood: people go from harmony to irritability or optimism to depression with no intermediate phases. In addition, in some cases the disease causes additional effects such as the appearance of different cognitive deficits.
According to the World Health Organization (WHO), bipolar disorder affects around 45 million people around the planet. Its symptoms, mainly the alternation of manic and depressive episodes separated by periods of normal mood, usually begin to manifest between 15 and 25 years of age.
A protein is the key
Although specialists already knew that this disorder is linked to many genes, each of which makes small contributions to the disease, they did not know exactly the biochemical process that generates the effects that characterize the disease. Now, the new study appears to have found the keys to this mechanism.
The backbone of the process appears to be Akt kinase, a type of protein that adds tags from the phosphate molecule to other proteins. These labels can function as on or off “switches”, modifying the functioning of other proteins and, ultimately, generating a direct influence on vital processes.
In neurons, this influence can lead to changes in the sending of signals between cells, a change capable of affecting thinking and mood. When the Akt pathway is accelerated, a large number of proteins obtain phosphate labels, while when the mechanism is slowed down, phosphate labels are absent or scarce.
The researchers found that people with bipolar disorder have reduced activity in this biochemical pathway, in a region of the brain crucial for attention and memory. Meanwhile, by interrupting the Akt pathway in rodents, the scientists observed memory problems and loss of key brain connections, something very similar to what happens in humans with bipolar disorder.
Related Topic: Schizophrenia and bipolar disorder share a genetic variant.
In human brain tissues
Advancing the research, the scientists analyzed brain tissues of deceased people with schizophrenia and bipolar disorder with and without psychosis. The objective was to search for phosphate tags, to thus identify the degree of reduction of the Akt pathway.
The initial hypothesis was that the greatest decrease would be found in people with schizophrenia, given their genetic relationship with this biochemical process. However, the results were clear and convincing: the group with the lowest expression of the Akt pathway was made up of men with bipolar disorder without psychosis. This allowed us to verify the strong relationship between the Akt protein and bipolar disorder.
For Michael Cahill, director of the research group that conducted the study published in the journal Neuron, “the loss of function of the Akt pathway in people with bipolar disorder is probably contributing to cognitive decline. The idea is that maybe we can introduce new drug strategies to help alleviate the core symptoms of bipolar disorder, “he said.
Akt-mTOR hypoactivity in bipolar disorder gives rise to cognitive impairments associated with altered neuronal structure and function. Amanda M. Vanderplow, Andrew L. Eagle, Bailey A. Kermath, Kathryn J. Bjornson, Alfred J. Robison and Michael E. Cahill. Neuron (2021) .DOI: https: //doi.org/10.1016/j.neuron.2021.03.008
Photo: Iulia Mihailov on Unsplash.