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Studies on the Molecular Mechanism of Brain Injury Induced by Drinking Water Fluorosis

Author: ZhuWenJing
Tutor: ZhangZiGui
School: Zhejiang Normal University
Course: Zoology
Keywords: Chronic fluorosis Hippocampal PSD-95 Learning and Memory Membrane fluidity
CLC: R599
Type: Master's thesis
Year: 2010
Downloads: 60
Quote: 1
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Abstract

Although fluoride is one of the essential trace elements, but the long-term excessive intake can cause chronic fluoride the poisoning (Chonic fluorosis). Performance of fluoride toxicity on the central nervous system to influence the children's intellectual development, inhibition of spontaneous neural activity, damage to learning and memory ability. The hippocampus is a key brain areas closely associated with learning and memory, is also one of the target site fluorine neurotoxicity. It has been proved that excessive fluoride can damage the hippocampus synaptic ultrastructure, but uncommon fluorine affect synaptic protein reported. Postsynaptic density protein 95 (postsynaptic density95, PSD-95) is one of the major protein of the postsynaptic density does not have activity, N-methyl-D-day (door) aspartate (N-methyl -D-aspartate, NMDA) receptor is associated with learning and memory protein. PSD-95 can be provided by the different structural domains string set NMDA receptor-related molecules, and the formation of signaling complexes excitatory signal transduction and integration in the synaptic level. The NMDA receptor plays a critical role in synaptic plasticity. We speculate that the changes in the level of expression of PSD-95 may affect the NMDA receptor cluster, thereby affecting learning and memory abilities of animals. The doctrine of free radical damage is recognized as one of the pathogenesis of fluorosis. The doctrine that, under normal circumstances, the body due to the variety of antioxidant enzymes (such as superoxide dismutase superoxide dismutase, SOD) and the presence of antioxidants (such as vitamin C), the production of free radicals and clear in a state of dynamic equilibrium. Fluorosis occurs in vivo lipid peroxidation enhanced oxidation system and antioxidant balance destruction, resulting in lipid peroxidation product malondialdehyde (malondialdehyde, MDA) content increased. SOD, MDA is the detection of commonly used indicators of the level of lipid peroxidation, but due to a variety of factors, the specificity and sensitivity. Thus, this experiment by copying the animal model of chronic fluorosis observed macroscopic chronic fluorosis on cerebral function, a better selection of specificity and sensitivity of micro spin labeling method detects brain oxidative stress level, and by immunohistochemistry (immuno-histochemical stain, IHC) to detect the protein expression levels of PSD-95 in hippocampal CA3 region. Through research, intended to screen out the brain of learning and memory-related brain areas (hippocampus) of fluorosis associated protein and factor (target molecules), and provide certain theoretical basis for further research on fluoride molecular biological mechanisms of toxic effects on the central nervous system, is a fluorine to provide a scientific basis for the early diagnosis and early treatment of poisoning, and thus broaden the develop a reasonable comprehensive treatment program ideas for the province fluoride contaminated area drinking water type fluorosis patients. Methods: 192 weanling male SD rats were randomly divided into four groups, namely the control group (drinking tap water, the water fluoride content is less than 0.5mg / L), low fluoride group (drinking water containing sodium fluoride (NaF) 15mg / L), in the fluoride group (drinking water containing NaF30mg / L), high fluoride group (60 mg / L of drinking water containing NaF). Each group prepared solution as drinking water, the only source of free access to food and drinking water, feeding time for 18 months. Every three months in the experiments on animal behavior detection detect spontaneous activity of rats and explore the behavior of the opening acts, the water maze spatial learning and memory; (9 months), respectively, in the mid-exposed to fluoride and exposed to fluoride (18 months) after the end of the two batches were decapitated rats, HE staining for the pathology observed in hippocampal CA3 region, spin labeling assay synaptosomal membrane fluidity changes, immunohistochemistry assay hippocampal CA3 region of PSD- 95 protein expression changes. Results: 1 opening act results show chronic fluorosis rats inhibited spontaneous activity in the the new synonym environment in running decrease in the number of cells (p lt; 0.05), standing frequency lower (p lt; 0.05 or p lt ; 0.O1). The results of the water maze exposed to fluoride rats search platform incubation period, the total distance of the search platform is generally higher than the rats with chronic fluorosis spatial learning and memory ability. Exposed to fluoride concentrations greater the longer the exposure time, the more obvious this toxic effect of fluoride. Synaptosomal membrane fluidity test results showed that with the synaptosomal membrane order parameter values ??,16-DSA labeled exposed to fluoride concentration increases with the rotational correlation time showed an increasing trend (p lt; 0.05 or p lt; 0.01 ), that hippocampal synaptosomal membrane fluidity gradually reduced. Chronic fluorine poisoning can lead to changes in membrane fluidity, 18 rats exposed to fluoride membrane fluidity change is more significant than the nine month group exposed to fluoride. It is worth noting that the nine-month high fluoride exposed to fluoride in the hippocampal synaptic membrane order parameter for the rotational correlation time falling instead of rising, basically back to the level of the low-fluoride group. 3, HE staining showed that chronic fluorosis rat hippocampal pyramidal cells reduced cell number, cell outline disappears cell vacuoles. IHC results showed that the expression levels of PSD-95 showed a decreasing trend with the increase in the concentration of exposed to fluoride, p lt; 0.05 or p lt; 0.01, compared with the control group of the same age. Prompted chronic fluoride poisoning can damage hippocampal neurons, lowered postsynaptic dense protein PSD-95 expression levels affect NMDA receptor complex cluster, so the decline in learning and memory abilities. 4, in the normal aging process in rats exist reduced increasing age of spontaneous activities, learning and memory abilities reduce the decline in membrane fluidity. Dyed different concentrations of fluoride exacerbate this trend, seen animal learning and memory behavior is influenced by multiple factors, aging and environmental factors (chronic fluoride poisoning) caused by oxidative stress can be caused macro animal learning and memory damage, micro impact decrease in synaptosomal membrane fluidity and PSD-95 expression levels decline. In summary, the rats drinking chronic fluorosis inhibit spontaneous neural activity, the damage spatial resolution of learning and memory ability; fluorine through the blood - brain barrier, attacks nerve cell membranes, resulting in synaptosomal membrane fluidity reduced, causing a reduction in postsynaptic density protein PSD-95 expression, this may be drinking type of chronic fluorosis brain injury caused by one of the molecular mechanism. According to the doctrine of free radical damage, oxidative stress may be involved in this series of toxic effects of fluoride. In view of the sensitivity of PSD-95 for chronic fluorosis, you can further study of animal development, the impact of the early fluoride on the expression levels of PSD-95 biomarkers of brain injury caused by study provides a theoretical basis for the screening of the brain fluorine.

Studies on the Molecular Mechanism of Brain Injury Induced by Drinking Water Fluorosis

Abstract

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