Memantine ameliorates the impairment of hippocampal long-term potentiation in olfactory bulbectomized mice.

Abstract

Alzheimer's disease (AD) is a neurological disorder characterized by cognitive deficit and loss of memory. Decreased in the levels of nicotinic acetylcholine (nAChR) and NMDA receptors (NMDAR) were found in AD, implicating in memory deficit. In addition, the expression level of calcium/calmodulin-dependent protein kinase II (CaMKII) decreases in the hippocampal CA1 region of AD patients. We have reported that impairment of NMDAR function and CaMKII activity in the hippocampal CA1 region was associated with memory deficit observed in olfactory bulbectomized (OBX) mice (J. Neurochem. 2006). Unlike other AD drugs, memantine blocks NMDAR channel and binds at near its Mg2+ site. e performed the behavioral analyses including Y-maze, novel object recognition and passive avoidance tasks and electrophysiological analyses for recording the long-term potentiation (LTP) in the hippocampal CA1 region in OBX mice. We first examined whether memantine ameliorates the impairment of cognitive function in OBX mice. In the behavioral analyses, memantine significantly improved the impairment of cognitive functions in OBX mice by Y-maze and novel object recognition tasks but not passive avoidance task. In addition, memantine significantly recovered the impairment of LTP in the hippocampal CA1 region from OBX mice. We also confirmed restoration of the activities of protein kinases such as CaMKII and PKC related to LTP induction by immunoblot analyses. These data suggested that memantine ameliorates cognitive deficits in OBX mice through the stimulation of LTP-related protein kinases.