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OBJECTIVES: Alzheimer’s disease (AD) is a severe neurodegenerative disease with presentation of the neuronal death, memory loss and cognitive decline. The relationship between neuroinflammation and AD has been well documented. However, the options of antiinflammatory treatment are very limited in patients with AD. Previous studies showed that flavonoids might be an effective treatment and thymoquinone (TQ), an aromatic hydrocarbon found in Nigella sativa suggested as a candidate molecule due to having strong anti-inflammatory effects. Our study aimed to investigate the effects of TQ on neuroinflammation and neuroprotection in Aβ(1–42) infused rat model of AD.
METHODS: A rat model of AD was established in 6 month-old rats (n = 23) by intra-hippocampal infusion during 14 days via a micro-osmotic pump containing aggregated Aβ(1–42). After model establishment, TQ at a dosage of 20 mg/kg/day was intubated intragastrically for 15 days. The functional recovery was determined using the Morris Water Maze task by measuring memory consolidation. The content of cytokine levels of Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-1 alpha (IL-1α) and Interferon-gamma (IFN-γ) in the hippocampus was assessed by Magnetic Luminex assay. In order to reveal the functional molecular changes in hippocampal tissue upon TQ administration, the protein expression profile of neuronal migration protein Doublecortin (DCX), synaptic plasticity marker Mitogen Activated Protein Kinase2 (MAP2) and apoptosis related protein Poly (ADP-ribose) Polymerase (PARP) was analyzed by Western blotting.
RESULTS: Aβ(1–42) infused group had worse memory performance than sham control group on Day 4 with an amelioration in this behaviour by TQ. In our study, the levels of TNF-α, IL-1α and IL1β did not significantly alter among groups. On the other hand, Aβ(1–42) infusion slightly decreased the level of IFN-γ compared to sham control group. TQ treatment ameliorated both impaired memory performance and IFN-γ levels. It was found that TQ treatment increased the protein levels of DCX compared to the sham control group. Also, the levels of MAP2 and the activation of PARP protein markedly decreased in both Aβ(1–42) and Aβ(1– 42)+TQ groups compared to the sham control groups Pearson’s correlation test showed a positive relation between IL-1β and DCX in the Aβ(1–42) group.
DISCUSSION: Our data suggested that TQ-related functional improvement might result from the increasing level of neurogenesis and ameliorating the level of IFN-γ in the Aβ(1–42) infused rat model of AD.