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Detrimental Effects of Sodium Fluoride on the Expression of Insulin Receptor in the Olfactory Bulb and Hippocampus of Male Mice.Abstract
Fluoride exposure is associated with lowered cognitive function ability, intelligence quotient, and mental decline, especially in children. The brain insulin receptor (IR) signaling system is related to neuronal plasticity and consequent cognitive ability. In our previous study, NaF exposure decreased IR expressions in olfactory bulb (OB) and hippocampus after Y-maze test in male mice. In order to further explore whether the Y-maze test affected IR gene and protein expression levels in the OB and hippocampus under the NaF exposure, healthy male mice were randomly allotted into four groups and challenged with 0, 50, 100, and 150 mg/L NaF for three continuous months. The results showed that femur fluorine content of the NaF-exposed groups increased significantly in a dose-dependent manner. NaF significantly decreased brain protein content and organ coefficient of the treated male mice. The protein and mRNA expression levels of the IR were significantly decreased in the OB and hippocampus of the NaF-treated mice. Interestingly, indicators (brain protein content and organ coefficient) measured in the present study were significantly lower than our previous study indicators (mice tested Y-maze test), especially the expression levels of IR protein and mRNA in the same concentration groups. Taken together, these results indicated that Y-maze test could promote the expression levels of IR protein and mRNA in the OB and hippocampus, while NaF had a stronger inhibitory effect, which resulted in adverse effects on the expression levels of IR in the OB and hippocampus of male mice.
References
-
Niu R, Chen H, Manthari RK, Sun Z, Wang J, Zhang J, Wang J (2018) Effects of fluoride on synapse morphology and myelin damage in mouse hippocampus. Chemosphere 194:628–633
-
Li J, Shi Y, Fan H, Li Y, Zhu Y, Lin X, Zhang J (2018) Effects of fluoride on surface structure of primary culture Leydig cells in mouse. Biol Trace Elem Res 183(1):123–127
-
Zhao Y, Li Y, Gao Y, Yuan M, Manthari RK, Wang J, Wang J (2018) TGF-?1 acts as mediator in fluoride-induced autophagy in the mouse osteoblast cells. Food Chem Toxicol 115:26–33
-
Yuan J, Li Q, Niu R, Wang J (2019) Fluoride exposure decreased learning ability and the expressions of the insulin receptor in male mouse hippocampus and olfactory bulb. Chemosphere 224:71–76
-
Doull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR, Thiessen KM, Webster TF (2006) Fluoride in drinking water: a scientific review of EPA’s standards. National Academies Press, Washington
-
Sun Z, Wei R, Luo G, Niu R, Wang J (2018) Proteomic identification of sperm from mice exposed to sodium fluoride. Chemosphere 207:676–681
-
Ma Y, Zhang K, Ren F, Wang J (2017) Developmental fluoride exposure influenced rat’s splenic development and cell cycle via disruption of the ERK signal pathway. Chemosphere 187:173–180
-
Wang J, Zhao Y, Cheng X, Li Y, Xu H, Manthari RK, Wang J (2018) Effects of different Ca2+ level on fluoride-induced apoptosis pathway of endoplasmic reticulum in the rabbit osteoblast in vitro. Food Chem Toxicol 116:189–195
-
Niu R, Sun Z, Cheng Z, Li Z, Wang J (2009) Decreased learning ability and low hippocampus glutamate in offspring rats exposed to fluoride and lead. Environ Toxicol Pharmacol 28:254–258
-
Ding Y, YanhuiGao SH, Han H, Wang W, Ji X, Liu X, Sun D (2011) The relationships between low levels of urine fluoride on children’s intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China. J Hazard Mater 186:1942–1946
-
Hussain J, Hussain I, Sharma KC (2010) Fluoride and health hazards: community perception in a fluorotic area of Central Rajasthan (India): an arid environment. Environ Monit Assess 162:1–14
-
Trivedi MH, Sangai NP, Patel RS, Payak M, Vyas SJ (2012) Assessment of groundwater quality with special reference to fluoride and its impact on iq of schoolchildren in six villages of the Mundra region, Kachchh, Gujarat, India. Fluoride 45:377–383
-
Poureslami HR, Horri A, Garrusi B (2011) A comparative study of the IQ of children age 7–9 in a high and a low fluoride water city in Iran. Fluoride 44:163–167
-
Basha PM, Madhusudhan N (2010) Pre and postnatal exposure of fluoride induced oxidative macromolecular alterations in developing central nervous system of rat and amelioration by antioxidants. Neurochem Res 35:1017–1028
-
Fang F, Gao Y, Wang T, Chen D, Liu J, Qian W, Cheng J, Gao R, Wang J, Xiao H (2016) Insulin signaling disruption in male mice due to perinatal Bisphenol A exposure: role of insulin signaling in the brain. Toxicol Lett 245:59–67
-
Plum L, Schubert M, Bruning JC (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16:59–65
-
Candeias E, Duarte AI, Carvalho C, Correia SC, Cardoso S, Santos RX, Placido AI, Perry G, Moreira PI (2012) The impairment of insulin signaling in Alzheimer’s disease. IUBMB Life 64:951–957
-
Bedinger DH, Adams SH (2015) Metabolic, anabolic, and mitogenic insulin responses: a tissue-specific perspective for insulin receptor activators. Mol Cell Endocrinol 415:143–156
-
Kleinridders A, Feeris HA, Cai W, Kahn CR (2014) Insulin action in brain regulates systemic metabolism and brain function. Diabetes 63:2232–2243
-
Ye L, Maji S, Sanghera N, Gopalasingam P, Gorbunov E, Tarasov S, Epstein O, Klein-Seetharaman J (2017) Structure and dynamics of the insulin receptor: implications for receptor activation and drug discovery. Drug Discov Today 22:1092–1102
-
De Felice FG (2013) Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 123:531–539
-
Chan AY, Swaminathan R, Cockram CS (1989) Effectiveness of sodium fluoride as a preservative of glucose in blood. Clin Chem 35:315–317
-
Shepherd GM, Chen WR, Greer CA (2004) The synaptic organization of the brain, Oxford Univ. Press 5:165
-
Bagley J, Larocca G, Jimenez DA, Urban NN (2007) Adult neurogenesis and specific replacement of interneuron subtypes in the mouse olfactory bulb. BMC Neurosci 8:92
-
Genuis SJ, Kelln KL (2015) Toxicant exposure and bioaccumulation: a common and potentially reversible cause of cognitive dysfunction and dementia. Behav Neurol 2015:1–10
-
Fox MA, Chen RS, Holmes CS (2003) Gender differences in memory and learning in children with insulin-dependent diabetes mellitus (IDDM) over a 4-year follow-up interval. J Pediatr Psychol 28:569–578
-
Dixon-Salazar TJ, Fourgeaud L, Tyler CM, Poole JR, Park JJ, Boulanger LM (2014) MHC class I limits hippocampal synapse density by inhibiting neuronal insulin receptor signaling. J Neurosci 34:11844–11856
-
Yan X, Hao X, Nie Q, Feng C, Wang J (2015) Effects of fluoride on the ultrastructure and expression of type I collagen in rat hard tissue. Chemosphere 128:36–41
-
Ommati MM, Tanideh N, Rezakhaniha B, Wang J, Sabouri S, Vahedi M, Dormanesh B, Koohi Hosseinabadi O, Rahmanifar F, Moosapour S, Akhlaghi A, Heidari R, Zamiri MJ (2018) Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats? Andrology 6:199–213
-
Bohatyrewicz A (2001) Bone fluoride in proximal femur fractures. Fluoride 34:227–235
-
Yang S, Wang Z, Farquharson C, Alkasir R, Zahra M, Ren G, Han B (2011) Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun 410:910–915
-
Varol E, Icli A, Aksoy F, Bas HA, Sutcu R, Ersoy IH, Varol S, Ozaydin M (2013) Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis. Toxicol Ind Health 29:175–180
-
Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188:319–333
-
Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 233:236–251
-
Wang J, Ge Y, Ning H, Wang S (2004) Effects of high fluoride and low iodine on biochemical indexes of the brain and learning-memory of offspring rats. Fluoride 37:201–208
-
D’Cruz SC, Jubendradass R, Jayakanthan M, Rani SJA, Mathur PP (2012) Bisphenol A impairs insulin signaling and glucose homeostasis and decreases steroidogenesis in rat testis: an in vivo and in silico study. Food Chem Toxicol 50:1124–1133
-
Wickelgren I (1998) Tracking insulin to the mind. Science 280:517–519
-
Banks WA, Owen JB, Erickson MA (2012) Insulin in the brain: there and back again. Pharmacol Ther 136:82–93
-
Chen Y, Deng Y, Zhang B, Gong CX (2014a) Deregulation of brain insulin signaling in Alzheimer’s disease. Neurosci Bull 30:282–294
-
Zhao W, Chen H, Xu H, Moore E, Meiri N, Quon MJ, Alkon DL (1999) Brain insulin receptors and spatial memory. J Biol Chem 274:34893–34902
-
Park CR, Seeley RJ, Craft S, Woods SC (2000) Intracerebroventricular insulin enhances memory in a passive-avoidance task. Physiol Behav 68:509–514
Funding
This research was supported by National Natural Science Foundation of China (31,372,497, 31,672,623), Key Research and Development Plan Project of Shanxi Province (201903D321108), Higher School Teaching Reform Innovation Project of Shanxi Province (J2018079), and Science and Technology Innovation Fund of Shanxi Agricultural University (2016ZZ09).