Mental illness with cerebellar atrophy
Focused on the discovery of Ebp1 mutations in patients
After production of Ebp1-deficient experimental mice
Mutation injection confirmed schizophrenia
“Suggested association with cerebellar dysfunction
It will serve as a basis for finding a cure.”
A new discipline that studies the causes of psychosis at the genetic level is called ‘molecular psychiatry’. The medical community has thought of mental illness as a kind of psychological trauma caused by a large shock or excessive psychological stress at a young age. However, with the development of brain science, it has been further revealed that diseases can also occur from biological and chemical causes, such as brain cells and neurotransmitters. It has advanced into molecular-sized micro-nano medicine that goes deeper and analyzes even the genetic abnormalities of cells. As a result, it was found that there are many genetic causes, such as depression and autism, that are inherited from parents in addition to acquired causes. Therefore, the latest research to identify mental illness as a genetic defect is pouring in.
A Korean research team has newly discovered the causative gene of schizophrenia using this molecular psychiatric technique. It is expected to serve as a valuable basic clue in uncovering the new course of onset and treatment of schizophrenia, which is a representative symptom of cerebellar atrophy, breaking away from studies that have focused on cerebral research. The National Research Foundation of Korea announced on the 2nd that a research team led by Professor Ahn Ji-in of Sungkyunkwan University College of Medicine discovered ‘Ebp1’ as a new causative gene for the decrease in the size of the cerebellum in patients with schizophrenia. This study was published and selected as a cover paper in the online edition of the international scientific journal ‘Molecular Psychiatry’ on February 15th.
Schizophrenia is a neuropsychiatric disease called schizophrenia in the past. It is common enough to occur in 1% of the total population, but the cause and treatment are still unknown. Patients do not feel normal emotions and show symptoms such as auditory hallucinations and hallucinations, which often results in repetitive behaviors or excitability of persecution and grandiose delusions. The biggest characteristic of patients with schizophrenia is that the size of the cerebellum attached to the back of the cerebrum decreases. In addition to the function of regulating the body’s sense of balance and movement, the cerebellum has recently been revealed to have new functions that link cognition such as language and attention, and emotions such as fear and pleasure. A common report was that the cerebellum was atrophied and the number of Purkinje cells decreased as a result of magnetic resonance imaging (MRI) examination of patients with schizophrenia. Purkinje cells are the only neurons that release GABA (inhibitory neurotransmitter) from the cerebellar cortex, the outer layer of the cerebellum.
Prof. Ahn’s research team focused on the fact that the ‘Ebp1’ mutation is found in schizophrenic patients, and custom-born mice (mouses) with a brain-specific defect lacking the Ebp1 gene. Ebp1 mutation refers to a phenomenon in which protein transcription is terminated at amino acids 8 and 183. When Ebp1 was removed from neurons, the mouse cerebellum was not formed normally. In the experiment, it was confirmed that the size of the cerebellum decreased by 20% in the 21-day-old mice and the 6-month-old mice, when cerebellar development was completed. In addition, it was found that Purkinje cells, the main nerve cells of the cerebellum, decreased by 50%, accompanied by synaptic disruption and reduced mobility, and eventually showed symptoms of schizophrenia. Therefore, the research team defined Ebp1 as one of the epigenetic regulators that regulate the expression of other genes during the development of the cerebellum and Purkinje cells. They found that it contributes to the normal development of the cerebellum by regulating the expression of special proteins according to the developmental time of specific neurons.
To confirm this, the research team investigated the symptoms and motility of schizophrenia in mice born following injecting the wild-type Ebp1 and the mutant gene derived from a schizophrenia patient into the cerebellum of an Ebp1-deficient mouse intrauterine embryo, respectively, according to the cerebellar development time. As a result, it was confirmed that while the Ebp1 wild-type gene-injected mice had improved morbidity and motility, the mice injected with the mutant gene still showed symptoms of schizophrenia. Professor Ahn said, “It is meaningful to approach the etiology from a completely different point of view from previous studies and suggest that Ebp1 mutations are importantly related to schizophrenia and cerebellar dysfunction. will be,” he said.
Reporter Noh Seong-yeol [email protected]