The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats
Introduction
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, which is associated with memory and cognitive impairments especially in the elderly population. A relationship between neuroinflammation and neurodegenerative diseases such as AD has been well documented. There are many evidence showing the significant influence of immune systems on mental functions such as learning, memory and neuronal plasticity [1]. Additionally, inflammation has been evidenced as a major reasons of disturbed learning and memory [2], [3]. On the other hand, systemic inflammation has been reported to be accompanied with oxidative stress status, which the later also has a critical role in memory and learning impairments [4]. Previous findings showed that inflammation may cause dysfunction in central cholinergic system in both hippocampal tissues and cerebral cortex in rats [5]. On the other hand researcher found that acetylcholine receptor antagonists have a detrimental effect on memory and this fact was emphasized by studding on Alzheimer's patient [6].
Tissue damages and infection through activating of microglia can increase proinflammatory cytokines and mediators specially in hippocampus and eventually by neuronal dysfunction and defects in cell proliferation and differentiation of the neuronal progenitor cells can lead to suppressing of neurogenesis, memory, learning and long term potentiation (LTP) [7]. In addition, many studies have shown that inflammation induced by lipopolysaccharide (LPS) resulted in learning and memory impairments through releasing of pro-inflammatory cytokines and inducing of reactive oxygen species (ROS) production [8], [9]. There is also a good confirmation that oxidative stress contribute in the central nervous system (CNS) disorder pathogenesis and also in learning and memory impairments [10].
Thus it is suggested that protecting against the oxidative injury and use of agents with antioxidant, anti-inflammatory and acetyl cholinesterase (AchE) inhibitory properties can reverse the memory impairment. So researcher found that thymoquinone (TQ), the most active component of the volatile oil of Nigella sativa seed, is one of this agent and exert anti-inflammatory and neuroprotective effects [11], [12]. Traditionally and experimentally, Nigella sativa and TQ have been used for their therapeutic effects on many degenerative diseases like Parkinson, AD and schizophrenia [13], [14], [15]. Therefore, in the current study we aimed the effects of TQ on LPS induced learning and memory impairments, hippocampal cytokine level and brain tissues oxidative damage in rats.
Section snippets
Animals
Twelve weeks-old male Wistar rats (240 ± 10 g) were purchased from local animal house located in Mashhad University of Medical Sciences, then accommodated in groups of 5 in individually ventilated cages and kept under standard conditions (temperature 22 ± 2 °C, humidity of 54 ± 2% and 12 h light/dark cycle). Food and water were freely available. The Ethical Committee of Animal Research approved the experimental procedures.
Chemicals and groups
LPS (Sigma-Aldrich Chemical Co) freshly dissolved in sterile saline prior to
The results of Morris water maze
According to the results of MWM test, training was associated with a reduction in the escape latency in all animals. Fig. 1A demonstrates a significant difference in the elapsed time across the 5-day training period between LPS and control groups (P < 0.05–P < 0.01). Additionally, MWM results demonstrated that the animals of LPS group didn’t remember location of the platform when they were examined in the probe trial. The LPS group spent lower time in the target quadrant compared to control group (P
Discussion
The present investigation aimed at elucidating mechanistically the possible protective effects of TQ against LPS-induced spatial and non-spatial memory impairments in rats. Although different mechanisms may contribute to create memory impairment, it has been clarified in recent years that inflammation plays a key roles in this process [22]. Inflammation of the brain has been suggested to induce tissue damages through increasing of activity of microglia and astrocytes in the brain [23]. LPS, the
Conclusion
In conclusion, the results of current study indicated that TQ improves learning and memory impairments induced by LPS in rats. Moreover, the effects of TQ are accompanied with attenuating hippocampal cytokine levels and improving of oxidative damage biomarkers in the brain tissues.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
The results are part of a M.Sc. student’s thesis. The authors appreciate the Vice Chancellor for Research and Technology, Mashhad University of Medical Sciences for financial support (grant No. 940755).
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