ИСТИНА

Alzheimer's disease is the most common cause of dementia. Despite numerous studies of its pathogenesis, processes leading to memory decay in Alzheimer's disease and tactics for its prevention are still in infancy. Here we propose a new hypothesis of memory autodegradation process in the brain compromised by neurodegeneration. A retrieval of an old consolidated memory, especially under conditions of novelty can render it to a labile form. This requires subsequent repeated consolidation, or reconsolidation. We argue that when an old memory is retrieved in the brain where reconsolidation processes are impaired by neurodegeneration, the original memory does not stabilize and degrades. Thus, being activated in a pathologically altered brain, memory trace weakens itself. If this suggestion is correct, then autodegradation of old memory in the impaired brain can be prevented by inhibiting its labilization during the retrieval. We started testing this hypothesis by employing a behavioral model of memory deficit produced by pharmacological impairment of memory reconsolidation in a one-trial passive avoidance learning model in young chicks (Gallus gallus domesticus). In previous experiments we demonstrated that retrieval of the passive avoidance memory paired with administration of a protein synthesis inhibitor anisomycin (ANI) or a glycosylation inhibitor 2-deoxygalactose (2DGal) resulted in the recall deficit. Here, we tested whether this memory impairment could be rescued by prevention of the memory labilization process. Two-days old chicks were trained in the passive avoidance learning model. Two hours after the training they were presented with a reminder paired with bilateral intraventricular administration of ANI (80 mkg) or 2DGal (3.28 mg) 5 min prior to the reminder. Additionally, 30 min before the reminder the animals received systemic administration of a non-competitive NMDA receptors antagonist MK801 (0.3 mg/kg) in order to access the possibility to prevent memory labilization and its effect. The control groups received physiological saline intraventricularly and intraperitoneally. The avoidance recall was tested 2 h after the reminder. The avoidance recall was significantly impaired in the animals which received ANI or 2DGal 5 min before the reminder as compared with control groups receiving no reminder or reminder coupled with physiological saline injection. Thus, inhibition of protein synthesis or glycoprotein fucosylation prevented reconsolidation of the reactivated memory producing amnesia. However, administration of NMDA antagonist MK801 prior to the inhibitor/reminder treatment prevented memory impairment resulting in high avoidance level that did not differ from the control groups recall. Thus, we have shown that memory deficit produced by memory retrieval under conditions of impaired protein synthesis can be protected by the preceding administration of NMDA receptor antagonist. We suggest that this effect might be due to prevention of reminder-induces memory trace destabilization which preserved the integrity of the original memory trace.