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.

The rapid development of industry has led to severe cadmium (Cd) pollution. Recent studies highlight that heavy metals, such as cadmium, accumulate within the food chain, exacerbating the public health crisis associated with these toxic substances. The health effects of cadmium exposure can manifest in both short-term and long-term contexts, significantly impacting various bodily systems. Cadmium accumulation has been correlated with neurotoxic effects that impair cognitive functions and motor skills, ultimately diminishing quality of life. The neurotoxicity of Cd is complex – it affects neurons, astrocytes, and microglia, resulting in the disruption of central nervous system homeostasis. Cadmium activates microglia and induces inflammation in astrocytes primarily through the TLR4/NF-kB pathway, leading to increased production of TNF-α and IL-6. The neurotoxic effects of Cd are also a result of increased oxidative stress, apoptosis initiation in astrocytes, and Cd-induced changes in mitochondrial function. Chronic Cd exposure may promote the aging of microglial cells. Microglia and astrocytes are in constant communication, a change in the function of one drives the dysfunction of the other, exacerbating inflammatory and apoptotic processes in glial cells. Additionally, due to the direct cooperation between glial cells and neurons, this will contribute to neuronal dysfunction, which may be associated with the development of neurodegenerative diseases. Future research on Cd toxicity in glial cells is needed to enhance our understanding and develop effective mitigation strategies.