The Effect of Prenatal and Neonatal Fluoride Exposure to Morphine-Induced Neuroinflammation

Abstract

Physical dependence is associated with the formation of neuroadaptive changes in the central nervous system (CNS), both at the molecular and cellular levels. Various studies have demonstrated the immunomodulatory and proinflammatory properties of morphine. The resulting neuroinflammation in drug dependence exacerbates substance abuse-related behaviors and increases morphine tolerance. Studies prove that fluoride exposure may also contribute to the development of neuroinflammation and neurodegenerative changes. Morphine addiction is a major social problem. Neuroinflammation increases tolerance to morphine, and neurodegenerative effects caused by fluoride in structures related to the development of dependence may impair the functioning of neuronal pathways, change the concentration of neurotransmitters, and cause memory and learning disorders, which implies this element influences the development of dependence. Therefore, our study aimed to evaluate the inflammatory state of selected brain structures in morphine-dependent rats pre-exposed to fluoride, including changes in cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression as well as microglial and astroglial activity via the evaluation of Iba1 and GFAP expression. We provide evidence that both morphine administration and fluoride exposure have an impact on the inflammatory response by altering the expression of COX-1, COX-2, ionized calcium-binding adapter molecule (Iba1), and glial fibrillary acidic protein (GFAP) in brain structures involved in dependence development, such as the prefrontal cortex, striatum, hippocampus, and cerebellum. We observed that the expression of COX-1 and COX-2 in morphine-dependent rats is influenced by prior fluoride exposure, and these changes vary depending on the specific brain region. Additionally, we observed active astrogliosis, as indicated by increased GFAP expression, in all brain structures of morphine-dependent rats, regardless of fluoride exposure. Furthermore, the effect of morphine on Iba1 expression varied across different brain regions, and fluoride pre-exposure may influence microglial activation. However, it remains unclear whether these changes are a result of the direct or indirect actions of morphine and fluoride on the factors analyzed.

Optimization of Calcium Fluoride Crystallization Process for Treatment of High-Concentration Fluoride-Containing Semiconductor Industry Wastewater

“…× seed height) − 0.012620 upflow velocity 2 − 0.000050 calcium conc. 2 − 0.013133 seed height 2 (5) Here, the levels should be specified in the original units for each factor. The predicted values for different experimental conditions showed a high degree of similarity with the experimental results for fluoride removal (Table 1).…”

“…However, the discharge of high-concentration fluoride in wastewater from these industries can pose significant environmental and public health concerns [2]. Fluoride is an essential element in the human body, but when present in concentrations exceeding 5 mg/L, it can lead to severe toxicity, potentially causing health issues such as osteoporosis, arthritis and neurological damage [3][4][5]. Consequently, the treatment of fluoride ions from industrial wastewater has emerged as a pressing environmental challenge.…”