A chloro substituted organoselenium mitigates stress-associated memory impairment and hippocampal glutamatergic function in a repeated Forced Swim Stress Model

Neuroscience. 2024 Dec 17:563:110-116. doi: 10.1016/j.neuroscience.2024.11.007. Epub 2024 Nov 7.

Abstract

Stress is triggered by a threatening event that alters the regulation of emotion, behavior, and cognition. The effects of stress on memory in animal models are well-documented. Firstly, this study aimed to determine whether the repeated forced swim stress (FSS) protocol induces memory impairment comparable to single prolonged stress (SPS) in the Y-maze test. The second objective was to evaluate whether (p-ClPhSe)2 pretreatment mitigates stress-associated memory impairment and hippocampal glutamatergic neurotransmission in FSS-exposed mice. Mice subjected to FSS and SPS protocols reduced time spent in the novel arm of the Y-maze test compared to the control group, with no observed changes in locomotor or exploratory behavior. (p-ClPhSe)2 was administered to mice at a dose of 5 mg/kg, 30 min before the first forced swimming session on days 1 and 2. Mice underwent a Y-maze test, after which they were euthanized, and hippocampal samples were collected. (p-ClPhSe)2 pretreatment protected against the reduction in time spent in the novel arm by mice subjected to FSS. Repeated FSS exposure increased hippocampal protein levels of NMDAR subunits 2A, 2B, and EAAT1 compared to controls. (p-ClPhSe)2 pretreatment prevented this increase. In conclusion, (p-ClPhSe)2 mitigated stress-induced memory impairment in FSS-exposed mice, normalizing hippocampal NMDAR 2A, 2B, and EAAT1 protein levels.

Keywords: Memory; NMDAR; Organoselenium; Stress.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glutamic Acid / metabolism
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders* / drug therapy
  • Memory Disorders* / metabolism
  • Mice
  • Organoselenium Compounds* / pharmacology
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Stress, Psychological* / metabolism
  • Swimming*

Substances

  • Organoselenium Compounds
  • Glutamic Acid
  • Receptors, N-Methyl-D-Aspartate