Effect of Coumarin on Memory Retention, Tissue Index, and GABAA Receptor Gene Expression in the Hippocampus of Gonadectomized Adult Male Rats

Learning is essential for understanding mental disorders, normal behavior, and forgetfulness. In this regard, the hippocampus plays an important role in the learning process. It has been reported that gamma-aminobutyric acid (GABA) receptors in the hippocampus are involved in learning and memory mechanisms and some diseases, such as epilepsy and Alzheimerchr('39')s. This study aimed to investigate the effect of coumarin on retention, tissue index, and GABA type A receptor gene expression in the hippocampus of male gonadectomy rats.

The population of this study consisted of 40 Wistar rats, which were randomized into 5 groups (n=8 each). These groups included healthy without treatment, gonadectomized without treatment, gonadectomized receiving solvent or Dimethyl sulfoxide, and gonadectomized receiving coumarin at a dose of 3.5 mg/kg. The treatment was administered intraperitoneally once daily in 2 weeks. A shuttle box was used to test the memory retention of the rats. At the end of the research process, the rats were exterminated in accordance with research ethics. After removing the brains of rats, in each group, in four brains histology test was implemented with Niels staining, and in four other brains, the hippocampus was removed quickly. The hippocampi were placed inside the micro type and frozen with liquid nitrogen. Finally, a gene expression test was taken from the hippocampus using a real-time polymerase chain reaction.

Based on the findings, in the memory retention test of initial latency to enter the dark room (step through latency), the gonadectomy group showed a reduction, compared to the healthy group.  Moreover, a significant decrease was observed in the number of healthy hippocampal pyramidal neurons; however, GABAA gene expression showed no significant difference. In the gonadectomy groups receiving treatments with different doses of coumarin, the amount of STL  (Step Through Latency) and number of healthy pyramidal neurons in the memory retention test showed a significant decrease, compared to the gonadectomy group receiving solvent; nonetheless, a significant increase was revealed in the GABAA-α2 gene expression.

It can be concluded that Gonadectomy caused memory impairment and coumarin affects memory impairment by increasing the GABAA-α2 gene expression and decreasing the number of healthy hippocampal neurons.