A synergistic effect of magnesium ions and lambertianic acid amide in the regulation of NMDA-type glutamate receptors in pyramidal neurons of the hippocampus

Abstract

Although caused by different mechanisms, the most common neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as multiple sclerosis, epilepsy, and ischemic brain damage, may share a common pathway: abnormalities of ionotropic glutamate receptors, particularly, of the NMDA type. Drugs with a glutamatergic mechanism of action are currently being intensively developed for the treatment of cognitive disorders and neurodegenerative processes. The goal of this work is to study the effect of lambertianic acid amide on glutamatergic synaptic transmission. A functional integration of glutamate and nonneurotransmitter receptors of hippocampal pyramidal neurons has been analyzed. The plasma membrane receptors are prevalently involved in integration of the effects of selective signaling molecules (mediators) and numerous internal and external factors, as well as the sharing of signaling pathways. An examination of mouse hippocampal slices has shown that lambertianic acid amide does not interfere with the development of NMDA receptor-dependent synaptic potentiation and displays neuroprotective properties, normalizing the epileptiform activity triggered by the absence of an endogenous ion channel blocker (magnesium ions) of the NMDA receptor. Lambertianic acid extracted from the Siberian pine (Pinus sibirica R. Mayr) needles and galipot and its derivatives are presumably a promising source of drugs with a glutamatergic mechanism of action that are suitable for the treatment of cognitive disorders and neurodegenerative diseases.