For the first time, a research team at Niigata University discovered that vascular endothelial growth factor (VEGF) is strongly expressed in the cerebellum and occipital lobe affected by Minamata disease and disrupts cerebral blood vessels.In addition, antibody therapy that neutralizes VEGF improves the symptoms of model animals.It is an epoch-making achievement that leads to the elucidation of the pathophysiology of Minamata disease and the development of treatment.
Methylmercury poisoning is known as Minamata disease and Niigata Minamata disease in Japan, but it still occurs sporadically in developing countries in connection with gold mining.The only treatment in the early stage of onset (acute phase) is a chelating agent that excretes methylmercury from the body, but its effect is insufficient and it causes sequelae such as light-headedness and narrowing of the visual field, so it is necessary to develop an acute phase therapeutic drug. there were.However, it was unclear why the affected areas were the cerebellum, occipital lobe, and postcentral gyrus, which was the biggest mystery of Minamata disease.
The research team examined severe cases of Minamata disease and hypothesized that methylmercury impairs not only the previously reported nerve cells, but also the blood-brain barrier (barrier function of blood vessels).Therefore, we confirmed the expression of vascular endothelial growth factor (VEGF) in various parts of the brain using a rat acute-phase methylmercury poisoning model.
As a result, VEGF increased in the cerebellum and occipital lobe, which are damaged by Minamata disease, and its expression was particularly remarkable in the cerebellum. VEGF causes the breakdown of the vascular barrier function, but in fact, substances in the blood vessels leaked into the brain tissue in the cerebellum.Therefore, it was considered that harmful substances in the blood vessels associated with methylmercury poisoning leaked into the brain, causing neuropathy.In addition, when an anti-VEGF antibody that neutralizes the action of VEGF was administered to methylmercury poisoned rats, improvement was observed in impaired motor function (hindlimb crossing phenomenon).
In the future, we will study methods for suppressing VEGF, confirm the efficacy and safety of treatment for methylmercury poisoning, and connect it to clinical application.
