Mice with a model of schizophrenia were cured with nicotine

Oleg Lischuk, N+1

An international group of scientists in animal experiments confirmed the role of nicotine receptors in the development of brain disorders characteristic of schizophrenia and found that the introduction of nicotine eliminates these disorders. The results of the work are published in the journal Nature Medicine (Koukouli et al., Nicotine reverses hypofrontality in animal models of addiction and schizophrenia).

In schizophrenia and some other mental illnesses, there is a reduced activity of the prefrontal cortex, the brain structure responsible for higher cognitive functions. It is believed that this phenomenon (it is called hypofrontality) is associated with many symptoms of schizophrenia, such as impaired attention, memorization, understanding explanations and difficult decision-making.

The activity of the prefrontal cortex is modulated by the nicotine subtype of acetylcholine receptors (n-cholinergic receptors). Recent genome-wide association studies have revealed a single nucleotide polymorphism of the CHRNA5 gene (it encodes the α5 h-cholinergic receptor subunit) associated with an increased risk of both schizophrenia and tobacco addiction. However, exactly how this variant of the gene affects brain functions has not been shown.

To find out, the staff of the Pasteur Institute in Paris with colleagues from other universities created genetically modified mice with a similar variant of the human gene CHRNA5. Standard tests have shown that such animals have impaired socialization and the ability to filter information from the senses, which is also observed in people with schizophrenia.

Two-photon calcium imaging (a method of registering neural impulses) of the prelimbic cortex (part of the prefrontal cortex) of mice showed that in the presence of a human gene with polymorphism, the activity of pyramidal (main excitatory) neurons was reduced by about a quarter compared to healthy animals. This decrease in activity corresponds to hypofrontality in humans.

Activity of prefrontal cortex neurons in a mouse from the control group (left)
and mice with the mutant human gene CHRNA5 (right).

Having received confirmation of the important role of nicotine receptors in disorders of the prefrontal cortex, and also considering that about 90 percent of schizophrenics are heavy smokers, scientists decided to study the effect of nicotine on the brain of mice with a model of schizophrenia. With the help of an infusion pump, they maintained a nicotine concentration in the blood of animals similar to that observed in smokers.

After two days of such therapy, the activity of pyramidal neurons of the prefrontal cortex increased significantly and remained elevated for two weeks. Nicotine administration for one to two weeks increased the activity of these neurons to the level of healthy animals.

"The results obtained strongly suggest that nicotine or other n-cholinergic receptor agonists can normalize the activity of the prefrontal cortex and reduce some cognitive impairments observed in people with neuropsychiatric disorders," the authors write. In their opinion, the malicious smoking of patients with schizophrenia is a form of pharmacological self-medication.

The data also indicate that h-cholinergic receptor agonists may become a potential aid for neuropsychiatric diseases that are accompanied by hypofrontality (schizophrenia, bipolar disorders, substance dependence, and others). "This defines a completely new strategy for the development of drug therapy," said Uwe Maskos, the head of the study.

Earlier, Duke University researchers linked the development of schizophrenia with changes in the complex actin-binding protein Arp2/3, which is involved in the construction of the cellular skeleton and, in particular, in the formation of synaptic connections on neuronal dentrites. The role of complement system proteins in the occurrence of this disease has also been shown. You can read more about genetic studies of schizophrenia in our material.

Portal "Eternal youth" http://vechnayamolodost.ru  26.01.2017