Title : Changes in expression of metalloproteinase 2 and 9 and their inhibitors in the neurotoxic effects of fluoride
Fluorine is a strong neurotoxin which can decrease the intelligence quotient and cause problems with learning and concentration. The Extracellular Matrix (ECM) of the central nervous system serves as the environment for neurons and glial cells, and at the same time, it plays the role of a modifier of these cells. Changes in the structure and the functioning of synapses are caused by ECM enzymes. These enzymes, especially matrix metalloproteinases (MMPs), accompany both physiological processes, such as learning or memorizing, and pathological processes. Metalloproteinases 9 and 2 (MMP-9 and MMP-2) and the inhibitors of metalloproteinases-3 and -2 (TIMP-3 and TIMP-2) seem to be particularly interesting. There is no data regarding the influence of fluorine on the expression of these enzymes and their inhibitors in the brain.
In the research, the rats were exposed to sodium fluoride (50 mg/L) already in the prenatal period until they reached the age of three months. After this time, the hippocampus, prefrontal cortex, cerebellum, and striatum were collected. In all of the aforementioned structures, the expression of proteins MMP-9, MMP-2, TIMP-3 and TIMP-2 was carried out by means of ELISA, gene expression by qRT PCR and immunolocalization by immunohistochemistry and microscopic visualization.
On the basis of the results, it can be concluded that fluorine influences the expression of MMP-9, MMP-2, TIMP-3 and TIMP2. In the study group, a statistically significant expression of MMP-2 was observed in the prefrontal cortex, striatum, and cerebellum, and a decrease in the expression of MMP-9 was noted in the prefrontal cortex and cerebellum in relation to the control group. We also saw the difference between TIMP-3 and TIMP-2 levels in the study group compared to control.
Our research suggests that changes in the expression of metalloproteinases and their inhibitors in the brain, caused by fluorine, could be an important factor of neurotoxicity of fluorine. The disorders of neuroplasticity processes can be considered as a biochemical basis for the decrease in the intelligence quotient caused by fluorine.