Memantine induces expression of PLA2 genes in rat brain: Possible implications for reverse learning and memory of Alzheimer's disease patients

Abstract

Memantine, an aminodamantane, is a non-competitive NMDA receptor antagonist with strong voltage-dependence and fast kinetics. Unlike other drugs used to treat Alzheimer’s disease, memantine blocks NMDAR channels in a concentration, time and voltage-dependent fashion. Previous results of our group evidenced a correlation of PLA2 inhibition activity and the severity of clinical aspects of Alzheimer’s disease. Besides, in rat, the activity of PLA2 is required for memory retrieval and the inhibition of this activity in hippocampus was reported to impair memory acquisition. In mammalians, this important gene family is composed of >30 genes dispersed in throughout the genome in almost every chromosome. These genes code for a large number of proteins that can be divided into five main enzymatic subgroups. After screening for PLA2 genes expressed in the brain, using in silico databases, we investigated if these genes were modulated of memantine. For this, Wistar rats received memantine by gavage for a period of 30 days. After treatment the animals were sacrificed and mRNA samples of hippocampus and frontal cortex were used for quantification of Pla2 genes using qRT-PCR. The expression of specific Pla2 genes was significantly increased in both tissues evaluated. Our data does not prove that memantine has a direct effect over PLA2, however, we could demonstrate that PLA2 expression is activated after treatment with this drug. This information may be relevant to clarify its mechanism of action on both aspects: neuroprotection and reverse deficits in learning/memory.