Disruptions in the action of insulin, which cause the development of diabetes and obesity, may also directly contribute to mental diseases such as schizophrenia, according to scientists from the US in the journal PLoS Biology.
Researchers at Vanderbilt University Medical Center found that disturbances in insulin-mediated signaling in the brain cause symptoms similar to schizophrenia in mice. Their research explains the greater susceptibility of diabetics to mental and cognitive disorders and suggests new therapeutic strategies.
Dr. Aurelio Galli and his colleagues were the first to show that insulin, the hormone that regulates glucose metabolism in the body, also controls the levels of the important neurotransmitter dopamine in the brain.
Disturbed dopamine-mediated signaling underlies diseases such as depression, parkinsonism, schizophrenia, and ADHD.
In their latest work, scientists have linked the molecular mechanisms responsible for abnormal insulin and dopamine signaling in the brain and symptoms of schizophrenia.
Researchers bred mice with impaired insulin signaling in their neurons (the Akt protein responsible for transmitting insulin signal in cells was not working for them) and observed that rodents had symptoms similar to schizophrenia. Moreover, they found that these mice were depleted of dopamine in the brain and elevated levels of another neurotransmitter, norepinephrine. Changes in the level of these substances were associated with an increased level of the NET protein transporting them from the space of connections between neurons.
According to the researchers, increasing the level of the NET protein leads to a decrease in dopamine and its conversion into norepinephrine. Low levels of dopamine in the cerebral cortex contribute to cognitive impairment, depression and withdrawal symptoms associated with schizophrenia.
Administration of the inhibitor of the NET protein to mice restored normal levels of dopamine in the brain and normal behavior of the animals. According to Dr. Galli, the first clinical trials of this type of drugs in patients with schizophrenia are already beginning.
According to the researchers, signaling via insulin and the Akt protein is essential for the proper functioning of dopamine, norepinephrine and serotonin – monoamine neurotransmitters. Unfortunately, it can be easily disregarded – by type XNUMX diabetes, high-fat diet, medications – and thus increase the risk of mental illness for many people. (PAP)