A study of mitochondrial damage in Alzheimer s disease and the protective effects of crocin: dose pre-treatment and post-treatment with crocin have different therapeutic effects

Alzheimer s disease is the most common form of dementia among the elderly. This progressive neurodegenerative disorder affects regions of the brain that control cognition, memory, language, speech, and awareness. Crocin, as a potent antioxidant, has been proposed to be effective in the management of neurodegenerative disease.In this study, we wanted to understand whether crocin could be effective for the recovery of the memory deficit caused by intra-hippocampal injection of Amyloid beta-42 (Aβ-42) in rats. We also wanted to know whether crocin could prevent mitochondrial damage caused by Aβ-42. On the other hand, we wanted to examine whether there is a difference between crocin-preventative and therapeutic effects. We examined the memory deficiency of rats with the help of Morris water maze. Then, we determined different mitochondrial toxicity endpoints caused by Aβ-42, including mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity, and cytochrome c release. All of these parameters are upstream events of cellular apoptosis which justifies neurodegeneration involved in Alzheimer’s disease.Our results demonstrated that the behavioral signs of memory deficiency caused by Aβ-42 significantly (P<0.01) reduced by both pretreatment and post-treatment with crocin (30 mg/kg). Furthermore, crocin prevented all the Aβ-42 induced above referenced mitochondrial upstream toxic events leading to neuronal apoptosis.These results demonstrated that crocin is a promising preventive drug candidate in Alzheimer’s disease. Furthermore, it seems that these antioxidant and neuroprotective effects of crocin are better seen when the compound is pretreated beforehand rather than introduced afterward in Aβ-42 exposed mitochondria.

کلیدواژه ها:

Crocin ، Amyloid beta ، Alzheimer s disease ، Neuroprotection ، Isolated mitochondria