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Sub-chronic exposure to diazinon affects cognitive behaviors and amyloid precursor proteins expression in the hippocampus of male adult rats
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Masoomeh Dadkhah   , Salva Afshari , Medhi Asghari Azar , Elham Safarzadeh , Mehdi Sarailoo |
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Abstract: (326 Views) |
Introduction: Organophosphate pesticides such as diazinon (DZN) play a role in the development of psychological symptoms and memory deficits but their effects on the amyloid precursor proteins (APP) expression remain unclear.
Methods and Materials: Adult male Wistar rats (280 ± 200 gr) were randomly divided into control and DZN groups (n=8 per group). Fresh DZN was diluted in 0.9% saline and animals received DZN) 2 mg/kg (by using a gavage tube (0.5 ml/day) for 5 days per week for 12 weeks. The control group animals received a similar volume of normal saline. We used novel object recognition memory (NORM), open field test (OFT), and elevated plus-mazes (EPM) to assess memory and anxiety-like behaviors in rats. We also evaluated alteration in the levels of amyloid precursor protein (APP) and APP-like protein-2 (APLP2) by western blotting method. The expression of related genes in the hippocampus was also evaluated by real-time quantitative PCR to evaluate the expression of the related genes in the hippocampus. Data were analyzed using GraphPad Prism version 8 and an independent t-student test, represented as the mean ± SEM. P values of p < 0.05 were considered statistically significant.
Results: Chronic low levels of oral exposure to DZN below the threshold during adulthood, significantly increased anxiety-like behaviors (P=0.001). Furthermore, long-lasting exposure to DZN altered the APP and APLP2 expression (P=0.001) and genes correlated with AD progression (P=0.01), in brain areas associated with psychological and neurodegenerative disorders and spatial memory.
Conclusion: Our finding demonstrates that long-term exposure to low levels of DZN in adulthood stimulates APP degradation, which may contribute to poor cognitive outcomes. Given that APP plays a significant role in Alzheimer's disease pathogenesis, alterations in APP expression could contribute to dementia.
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| Keywords: Diazinon, Hippocampus, Novel object recognition memory, Anxiety-like behaviors, Amyloid precursor proteins |
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Full-Text [PDF 267 kb]
(47 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/11/16 | Accepted: 2023/08/23 | Published: 2023/08/23
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