Department of Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland.
Department of Biochemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland.
Int J Mol Sci. 2020 Dec 31;22(1):391. doi: 10.3390/ijms22010391.
Fluoride (F) exposure decreases brain receptor activity and neurotransmitter production. A recent study has shown that chronic fluoride exposure during childhood can affect cognitive function and decrease intelligence quotient, but the mechanism of this phenomenon is still incomplete. Extracellular matrix (ECM) and its enzymes are one of the key players of neuroplasticity which is essential for cognitive function development. Changes in the structure and the functioning of synapses are caused, among others, by ECM enzymes. These enzymes, especially matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in both physiological processes, such as learning or memory, and pathological processes like glia scare formation, brain tissue regeneration, brain-blood barrier damage and inflammation. Therefore, in this study, we examined the changes in gene and protein expression of MMP2, MMP9, TIMP2 and TIMP3 in the prefrontal cortex, hippocampus, striatum and cerebellum of rats (Wistar) exposed to relatively low F doses (50 mg/L in drinking water) during the pre- and neonatal period. We found that exposure to F during pre- and postnatal period causes a change in the mRNA and protein level of MMP2, MMP9, TIMP2 and TIMP3 in the prefrontal cortex, striatum, hippocampus and cerebellum. These changes may be associated with many disorders that are observed during F intoxication. MMPs/TIMPs imbalance may contribute to cognitive impairments. Moreover, our results suggest that a chronic inflammatory process and blood-brain barrier (BBB) damage occur in rats' brains exposed to F.
氟化物（F）暴露会降低大脑受体活性和神经递质的产生。最近的一项研究表明，儿童时期的慢性氟暴露会影响认知功能并降低智商，但这种现象的机制尚不完全清楚。细胞外基质（ECM）及其酶是神经可塑性的关键参与者之一，对于认知功能的发展至关重要。细胞外基质酶会引起突触结构和功能的变化，这些酶，尤其是基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs），参与学习或记忆等生理过程以及神经胶质瘢痕形成、脑组织再生、血脑屏障损伤和炎症等病理过程。因此，在这项研究中，我们研究了在出生前和新生儿期暴露于相对低剂量氟化物（饮用水中 50mg/L）的大鼠（Wistar）的前额叶皮层、海马体、纹状体和小脑中 MMP2、MMP9、TIMP2 和 TIMP3 的基因和蛋白表达变化。我们发现，出生前和出生后暴露于 F 会导致前额叶皮层、纹状体、海马体和小脑中 MMP2、MMP9、TIMP2 和 TIMP3 的 mRNA 和蛋白水平发生变化。这些变化可能与氟中毒期间观察到的许多疾病有关。MMPs/TIMPs 失衡可能导致认知障碍。此外，我们的结果表明，暴露于 F 的大鼠大脑中会发生慢性炎症过程和血脑屏障（BBB）损伤。
