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Nutr Neurosci. 2019 Feb 21:1-16. doi: 10.1080/1028415X.2018.1492772. [Epub ahead of print]

Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Author information

1
a Department of Pharmacodynamics and Toxicology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
2
b Pharmaceutical Research Center, Department of Medicinal Chemistry , Mashhad University of Medical Sciences , Mashhad , Iran.
3
c Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
4
d Pharmaceutical Research Center , Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad , Iran.

Abstract

Organophosphorus compounds are widely used in agriculture. Epidemiological studies propose that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are unclear. Here, we investigated the impact of malathion exposure on the cognitive ability and the underlying mechanisms in rats. Moreover, we studied whether crocin reduced malathion-induced cognitive and memory loss in rats. Malathion (100 mg/kg) and crocin (10, 20 and 40 m/kg) were administered into the rats once a day for 14 days via i.p. Also vitamin E was used as positive control. Malathion exhibited spatial memory deficits as assessed by Morris water maze (MWM). Malathion increased the latency to reach the platform and decreased time spent and swimming distance of animals in target quadrant in probe trial. These effects were protected by crocin. Malathion exposure induced spatial learning and memory deficits with a simultaneous decrease of PSD93 and TAU hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of protein phosphatase-2A (PP2A). Additionally, the elevation of malondialdehyde (MDA), TNF α and IL-6 levels, amelioration of reduced glutathione (GSH) in the hippocampus and reduction of plasma acetylcholinesterase activity were observed upon administration of the malathion. Also, malathion-induced apoptosis in the hippocampus. Crocin or vitamin E improved memory damages and antagonized the effects of malathion. According to the data of this study, crocin mitigated malathion-induced neurological alterations and cognitive impairment by reducing oxidative stress and inflammation, inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

KEYWORDS:

Apoptosis; Crocin; Lipid peroxidation; Malathion; Memory impairment; Morris water maze; TAU

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