Effects of thymoquinone and memantine alone and in combination on memory and hippocampal morphology in rats with streptozotocin-induced Alzheimer's disease

Turk J Med Sci. 2023 Aug;53(4):894-901. doi: 10.55730/1300-0144.5653. Epub 2023 Aug 18.

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Thymoquinone (TQ) has broad biological functions, including antiinflammatory, antioxidant, neuroprotective properties. Memantine (MEM) is indicated for the symptomatic treatment of moderate to severe AD. We aimed to evaluate the effect of TQ alone or in combination with MEM on memory and hippocampal morphology in an STZ-induced rat AD model.

Methods: Thirty male rats were included in this study. The AD model was created by giving ICV STZ. The rats were divided into 5 groups (n = 6 each). Group 1 (control group): The rats received only ICV-STZ 3 mg/kg for 2 weeks. Group 2 (sham group): In addition to ICV STZ, 9% NaCl, 1 mL/day i.p. for 2 weeks of injection, was applied. Group 3 (TQ group): In addition to ICV STZ, rats received TQ 10 mg/kg i.p. for 2 weeks. Group 4 (MEM group): In addition to ICV STZ, rats were given MEM at a dose of 5 mg/kg for two weeks. Group 5 (TQ+MEM group): In addition to ICV STZ, this group was given TQ (10 mg/kg/day, i.p.) and MEM (5 mg/kg/day, i.p.) for 2 weeks. On the 15th day, passive avoidance learning (PAL) was applied to all groups. Then, rats were sacrificed, neurons in the hippocampal CA1, CA2, CA3 regions were evaluated.

Results: Groups 3, 4, 5 had longer latency periods than groups 1 and 2. The neuron density in the CA1, CA2, CA3 regions had decreased in groups 1 and 2 compared to groups 3, 4, 5. There were significantly more neurons in groups 3, 4, 5 than in groups 1 and 2.

Discussion: We found that TQ alone and in combination with MEM showed ameliorative effects on memory and hippocampal morphology. TQ may offer a promising treatment strategy for AD.

Keywords: Alzheimer's disease; memantine; streptozotocin; thymoquinone.

MeSH terms

  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Animals
  • Disease Models, Animal
  • Hippocampus
  • Male
  • Maze Learning
  • Memantine / adverse effects
  • Neurodegenerative Diseases*
  • Rats
  • Streptozocin / adverse effects

Substances

  • Memantine
  • Streptozocin
  • thymoquinone

Grants and funding

This study was supported by the Tokat Gaziosmanpaşa University Scientific Research Projects Commission (BAP 2015/106).