Brain structure harmed by vitamin B1 deficiency can be recovered

Vitamin B1 plays a relevant role for good brain functioning, and chronic deficiency of this nutrient can generate a number of neurological and cognitive problems. This is because the lack of B1 in the body, for a prolonged period, leads to the death of neurons and other cells, compromising functions of different regions of the brain, including the hippocampus, the structure responsible for the constitution of new memories. Until then, scientific literature indicated that the parts of the brain injured due to lack of vitamin would be unrecoverable, but a study by Fiocruz Minas showed that it is possible to regenerate the hippocampus, associating B1 replacement with anti-inflammatory drugs. The findings were described in an article published in the Journal of Neuroinflammation, one of the most influential in the field of neurosciences.

Infographic explains the process

To arrive at the results, the researchers used slices of the hippocampus of rats, preserving, in the laboratory, all the components necessary for tissue functioning, except vitamin B1. The objective was to investigate the processes triggered by the lack of this nutrient. The research showed that, from the 5th day on, B1 deficiency was established, leading to the death of the cells that expend more energy, neurons. This first wave of cell death released components in the tissue, which activated the immune system and generated a potent inflammatory process that lasted a few days. When B1 deficiency left these inflammatory cells without energy and they began to lose activity, inflammation decreased.

As early as the 10th day, there was a pulse of neurogenesis, which is the production of new neurons. "We have seen that the slices of the hippocampus are repopulated with new mature neurons, so the activity of inflammatory cells decreases. This does not last long, but there is a time window in which it is still possible to recover the tissue", says Fiocruz Minas researcher Roney Coimbra, coordinator of the study.

With this result, the scientists moved on to a second stage, in order to verify whether the introduction of an anti-inflammatory drug would be able to trigger the production of neurons, so as to to prove the causal relationship between the reduction of inflammation and neurogenesis. For this purpose, the researchers introduced Resveratrol, a compound of natural origin known to attenuate inflammations and inhibit the activation of pro-inflammatory cells. The results showed that Resveratrol decreased the activity of the defense cells in the hippocampus slices, interrupting the inflammatory process. Neurogenesis therefore took place earlier.

"Defense cells do not die, but the action of Resveratrol is sufficient to inhibit inflammation and stimulate the repopulation of neurons. Our study therefore proved that a hippocampus harmed by vitamin B1 deficiency can be recovered by controlling inflammation. The results indicate a path for research into new therapeutic approaches, which combine B1 therapy with anti-inflammatory drugs capable of reducing inflammation and allowing natural tissue repopulation with new neurons", explains Coimbra.

For further validation of the findings, the research also included an investigation of the genes involved in the triggered processes. The analysis of genetic programming throughout the time series showed that the most active and less active genes were in accordance with what was being observed in the morphology of the hippocampus slices analyzed under a microscope. In addition, the study showed that there is the involvement of epigenetic mechanisms, which are the chemical changes that occur in proteins around which DNA wraps to form chromosomes.

According to the researchers, the results of the study open perspectives for the treatment of diseases such as Wernicke-Korsakof syndrome, which manifests as a consequence of non-ingestion, malabsorption or incorrect metabolization of vitamin B1 and is characterized by a combination of encephalopathy and psychosis, with cognitive deficits, amnesia, neuropathological disorders with extensive neurodegeneration, and cellular and molecular dysfunction in the hippocampus and other regions of the brain.

The causes of Wernicke-Korsakof syndrome are mainly related to alcoholism, and the prevalence of classic symptoms associated with the syndrome ranges from 2 to 3% in the population, and may exceed 10% in some groups. It is noteworthy that alcoholism has grown a lot during the pandemic, and the tendency is that there will be an increased incidence of chronic vitamin B1 deficiency and even Wernicke-Korsakof syndrome. Lesions caused by vitamin B1 deficiency can lead to death. The lethality rate is 17 to 20% of cases.

"Our study, albeit still in its laboratory phase, opens possibilities for the treatment of the disease in the future so as to not only stop neuronal death and the worsening of symptoms, through B1 replacement, but also allow the recovery of injured brain areas," the researcher said.

The work was developed in partnership with the Post-Graduation Program in Neurosciences of the Federal University of Minas Gerais (UFMG), being part of the master's thesis of student Larissa Cassiano.