Effects and underlying mechanisms of rosmarinic acid on event related potentials and oxidative stress changes in an experimental model of Alzheimer disease

Alzheimer's Disease (AD) is a common type of dementia characterized as a progressive defectiveness in cognition and behaviour. It is known that amyloid beta peptide (Aβ) polymerization and accumulation of amyloid fibrils play a role in the pathophysiology of Alzheimer's Disease. In the present study, we examined the effects of antioxidant properties of rosmarinic acid to the complications of AD by electrophysiological, histological and biochemical analysis. In our work, 100 wistar rats are divided randomly into four groups; Sham(S), Sham+ rosmarinic acid (SR), Aβ42 peptide (AH) and Aβ42 peptide+ rosmarinic acid (AHR) groups. Alzheimer model rats (AH and AHR) were administered with Aβ42 peptide (2,2 nmol/10µl) intracerebroventricularly. SR and AHR groups were received 50mg/kg/day rosmarinic acid via gavage for two weeks. At the end of the experimental period, auditory event related potentials were recorded and then histological and biochemical analysis were performed in the brain tissues. Increased TBARS and 4-HNE values were detected in Alzheimer group compared to the S and SR groups and rosmarinic acid decreased lipid peroxidation to the control levels in the AHR group. Furthermore, antioxidant enzyme activities (SOD, CAT, GSH-Px) were attenuated in the AH group, rosmarinic acid treatment was prevented this attenuation in the AHR group. Similarly, decreased GSH level in the AH group versus the S and SR groups was increased but not reached to the control level in the rosmarinic acid treated AHR group. Also, Aβ impaired the cholinergic system by reducing the amount of ACh and AChE activity, and rosmarinic acid reversed these effects in the AHR group. Beside, ultrastructural and immunohistochemical analysis showed histopathological alterations, significant Aβ deposition and astrocyte activation in the AH group. Attenuated Aβ deposition, astrocyte activation and preserved cell structure were observed in the AHR group. Electrophysiological results indicate that Aβ42 peptide can affect the auditory discrimination and ecoic memory processes, and the treatment of rosmarinic acid can improve the Aβ42 related alterations in these functions. In conclusion, our study clearly showed that Aβ42 peptide affect antioxidant-oxidant balance, cholinergic markers and neurol network dynamics of auditory processes and rosmarinic acid has curative effect on the alterations detected in these parameters.