Introduction of a Central ER Stress-Induced Spatial Memory Impairment in Rats: a Model for Studying Alzheimer’s Disease

Endoplasmic reticulum (ER) is a key cellular organelle involved in many physiological functions. One of the most important ER duties is proteinfolding. Debility of ER in this duty is known as ER stress. ER stress participates in a wide range of diseases including neurodegeneration diseases. Accumulation of misfolded protein in the ER of neurons is a common feature in Alzheimer’s disease (AD) to that extend thatAD is one of the protein misfolding disorders. But so far no model has been designed to make memory impairment similar to AD just by ER stress induction and in previous models of memory impairment, ER stress has been made indirectly. Therefore, the aim of thisstudy was to design a pharmacological AD like memory impairment model by induction of central ER stress. Materials and Methods: In order to induce central ER stress, different doses (5, 10 microgram) of Thapsigargin (TG) were administered to the male Wistar rats throughIntracerebroventricular (icv) injection. Cognitive function of animals was evaluated by Morris water maze test. As an indicator for ER stress, hippocampal CHOP protein was assessed by western blotting. Results: The results showed that TG impaired spatial dose-learningand memory in a dose-dependent manner. Meanwhile, molecular results also showed a concurrent increased level of hippocampal CHOP with memory impairment. Conclusion: This study introduces, for the first time, a pure ER stress induced model of memory impairment,which can be used as a basis for future studies on the role of ER stress in AD.