Mariam Chighladze
Akaki Tsereteli State University, USA
Title: Effects of chronic administration of Memantine on okadaic acid induced spatial short-term memory impairment
Biography
Biography: Mariam Chighladze
Abstract
Alzheimer’s Disease (AD) is a neurodegenerative disease that causes progressive cognitive and behavioral impairment in the elderly. It is widely believed that changes in the cerebral activity of protein phosphatases have been implicated in the pathogenesis of AD. Okadaic Acid (OA) is a potent and selective inhibitor of protein phosphatases. OA induced memory deficit and elevation of Ca2+ was found to be correlated with neurotoxicity and N-Methyl-D-Aspartate (NMDA) receptor emerged as a plausible link. According to available data, the NMDA receptor antagonists (including memantine) have the potential to perform the neuroprotective role in neurodegenerative processes caused by Ca2+ ionotoxicity. In the present study, the possible beneficial effect of memantine on the OA induced spatial short-term memory impairment was examined in spatial alternation task. OA was dissolved in artificial Cerebro-Spinal Fluid (aCSF) and injected Intra Cerebro Ventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into two subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline was given daily for 13 days starting from the day of OA injection. The behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory and chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutic targets for AD pathology.