Crocin Acting as a Neuroprotective Agent against Methamphetamine-induced Neurodegeneration via CREB-BDNF Signaling Pathway

Document Type: Research article

Authors

1 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences. Tehran, Iran.

2 Research Center for Addiction and Risky Behaviors (ReCARB), Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran.

3 Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Methamphetamine (METH) abuse causes neurodegeneration. Medicinal herb such as crocin has neuroprotective properties. The current study evaluates the role of CREB-BDNF signaling pathway in mediating the neuroprotective effects of crocin against METH-induced neurodegeneration in rats. Sixty adult male rats were divided randomly into group 1 and group 2 which received 0.7 mL/rat of normal saline and 10 mg/kg of METH intraperitoneally (i.p) respectively, and groups 3, 4, 5 and 6 which treated concurrently with METH (10 mg/kg) and crocin(10, 20, 40 and 80 mg/kg I.P respectively) for 21 days. Morris water maze(MWM)was used to evaluate cognitive activity. According to the critical role of hippocampus in cognitive behavior, the molecular and biochemical parts of our study were done in hippocampus and according to this, hippocampal neurodegenerative parameters and also CREB and BDNF levels were evaluated in isolated hippocampus. METH disturbed the learning, memory, and simultaneous treatment with various doses of crocin reduced the METH-induced cognition disturbances. In addition, METH treatment increased lipid peroxidation and the levels of oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and Bax, while reducing reduced form of glutathione (GSH), Bcl-2, P-CREB, and BDNF levels in the hippocampus. METH also reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in the hippocampus. In contrast, crocin (40 and 80 mg/kg) attenuated METH-induced apoptosis, oxidative stress, and inflammation, while elevating P-CREB and BDNF levels. Thus, crocin confers neuroprotection against METH-induced neurodegeneration in hippocampus and this is probably through activation of P-CREB/BDNF signaling pathway.

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