Comparing the Effect of Acute and Chronic Cyclophosphamide Administration on Cognitive and Avoidance Memories and Histopathology of the Hippocampus in Mice

Abstract

Background and purpose: The quality of life in patients with cancer is affected by cognitive changes after chemotherapy. There are different reports about the effect of cyclophosphamide as a chemotherapy agent on cognitive function. So, the present study aimed to investigate the effects of acute and chronic injections of cyclophosphamide on passive avoidance and novel object recognition memory in an animal model. Materials and methods: In this experimental study, 56 male mice (weighing 30±5g) were investigated in 8 groups, including a control group (saline) and a group that received cyclophosphamide with acute injection (single dose) and two similar groups with chronic injection (4 injections per week for 4 weeks) for passive avoidance test. In the next four groups the novel object recognition test was performed. Cyclophosphamide was injected at 50 mg/kg intraperitoneally and before training. In order to investigate the histopathology of the hippocampal tissue, the brains of the mice were removed after the tests. Data were analyzed applying independent t-test in SPSS. Results: Acute cyclophosphamide administration had no significant effect on the two types of memory, but in chronic injections, it decreased the passive avoidance memory (P<0.05), while it did not affect cognitive memory. Ischemic changes were observed in neurons CA1 to CA3 (Cornu Ammonis areas) and DG (Dentate Gyrus) hippocampal in chronic cyclophosphamide administration. Conclusion: Cyclophosphamide was not found to affect all aspects of memory, and the avoidance memory impairment due to its chronic administration seems to be due to neurological damage to the hippocampus.

Keywords

• cyclophosphamide
• passive avoidance memory
• new object recognition
• hippocampus