Developing Topics.

Background: Aβ accumulation is a key event driving neurotoxicity in Alzheimer's disease. Previously, we demonstrated that oligomers of amyloid beta (oAβ) induce an increase in the levels of APP and BACE1 in Rab11-positive endosomes, leading to the intracellular accumulation of Aβ1-42 in human neurons derived from iPSCs (HN-iPSCs). This vicious cycle of Aβ generation induced by Aβ itself, is pivotal for the propagation of pathology.

Changes in hippocampal arc protein expression and synaptic plasticity by the presentation of contextual cues linked to drug experience.

Contextual cues linked to drug experience have been frequently associated to craving and relapse, with this phenomenon being described in human and experimental animals. Hippocampal synaptic plasticity has been related to learning, memory, and adaptive processes developed during chronic administration of drug abuse. In this study, we investigated if the environmental context associated with withdrawal experience was able to evoke the same behavioral alteration observed after chronic benzodiazepine administration.

Participation of dorsal raphe nucleus in the behavioral alteration observed after discontinuation of chronic diazepam administration: possible neural circuitry involved.

Previous findings from our laboratory have demonstrated a positive correlation between the development of tolerance to diazepam (DZ) 5 mg/kg/day over 4 days, and increased hippocampal synaptic plasticity. It seems likely that a similar plastic phenomenon may occur on hippocampal formation after chronic (18 days) DZ administration. We postulate hippocampal long-term potentiation (LTP) underlying substrate to the behavioral alteration observed after chronic DZ administration.