Melatonin prevents amyloid protofibrillar induced oxidative imbalance and biogenic amine catabolism

Oxidative stress is one of the hypothesized pathogenic mechanisms for neurodegenerative diseases, including Alzheimer's disease (AD); numerous studies suggest that Aβ is toxic to neurons by free radical mediated mechanism. A constant feature in AD brain is selective neuronal loss, accompanied by dysfunction of several neurotransmitter systems, such as cholinergic, serotoninergic and noradrenergic systems. In the present study, we studied the neuroprotective role of melatonin against amyloid protofibrils and the toxicity of protofibrils on serotoninergic and noradrenergic systems. Mice were divided into four groups (n = 8 each), control, Scrambles Aβ35–25 treated, Aβ25–35 injected, and melatonin treated. A single dose of Aβ25–35 (25μg) was administered to mice via intraperitoneal injection. Melatonin (50 mg/kg body weight) was administered intraperitoneally for 3 days to the Aβ25–35 injected mice. Control mice received only physiological saline and Scrambles receives Aβ35–25 single intraperitoneal injection of 25 μg of Aβ35–25. Our study showed that melatonin significantly reduces reactive oxygen species (ROS) production in the astrocytes, lymphocytes and hepatocytes of Aβ injected mice by increasing the levels of scavenging enzymes, SOD, catalase and GSH when compared to the untreated group. Immunohistochemistry study reveals that melatonin prevents the activation of GFAP in neocortex and transcription factor NF-κB in liver and neocortex of Aβ injected mice. It also prevents the elevation of dopamine depletion and its degradation products. Thus, while melatonin may be a potential therapeutic agent in the prevention of oxidative stress associated with Aβ and AD, it can also prevent dopamine turnover induced by Aβ.