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CC chemokine 2 (CCL2), which is generally expressed in white blood cells and rarely expressed in normal nerve tissues, plays an important role in the innate immunity caused by tissue damage and some diseases. Numerous studies have found that CCL2 can damage the learning and memory of rats. In order to study the effect and mechanism of CCL2 on the learning and memory of rats, SD rats were divided into groups, injected into the hippocampus on both sides, and a Morris water maze experiment was performed a few days after the injection. , And then separated the hippocampus of each group of rats. The final study found that CCL2 can damage the learning and memory of rats. The mechanism is related to the involvement of inflammation, neuroexcitation toxicity, the decrease of ACh content, and the mediation of cell apoptosis.
Some researchers also explored the effects of CC-like chemokine ligand 2 on learning, memory and cognitive function in rats, and comprehensively explored its mechanism from four aspects of oxidative stress, inflammation, excitotoxicity and apoptosis.It was found that CCl2 in the dose range of 0.5-50ng impaired learning and memory in a dose-dependent manner.CCl2 in the dose range of 0.5-50ng impaired cognitive function in a dose-dependent manner.This study may provide a basis for the study of central pathogenic mechanism of CCl2.
Morris water maze experiment is a widely used experimental method to evaluate spatial learning and memory of animals in behavioral neuroscience. More and more studies have shown that the cerebral cortex, subcortical regions and hippocampus of rats play an important role in spatial learning and exploration strategies in Morris water maze experiment.Medicilon pharmacodynamics evaluation system covers neuropsychiatric system diseases, inflammatory and immune system diseases, metabolic diseases, cardiovascular and blood system diseases, digestive system and other diseases. For current focus of hot diseases such as NASH, Alzheimer’s disease, inflammatory and immune diseases, etc.Medicilon Pharmacology has extensive experience in the evaluation of new drugs and effective animal models to meet the different types of drug development needs of customers.
Some researchers have explored how naringin improves CCL2-induced learning and memory impairment in rats and its mechanism [1]. Researchers’ 56 SD rats were randomly divided into blank group, sham operation group, model group (CCL2), positive drug (CCL2+memantine) group, low naringin (CCL2+25 mg•kg-1 naringin), Medium (CCL2+50 mg•kg-1 naringin) and high (CCL2+100 mg•kg-1 naringin) dose groups. Except for the blank and sham-operated groups, all groups injected CCL2 into the hippocampus of rats by brain positioning to make learning and memory impairment models. Morris water maze was used to detect the learning and memory levels of rats in each group; HE staining was used to observe the morphology of neurons in the CA1 area of the hippocampus. Finally, the study found that naringin can significantly improve the learning and memory dysfunction caused by CCL2 in rats. The mechanism is related to the antioxidant and anti-apoptotic effects of naringin.
Researchers also explored the effect of Tanshinone A (TanA), the main component of traditional Chinese medicine Danshen, on improving cognitive dysfunction caused by CC chemokine ligand 2 and its mechanism. The researchers randomized 56 male SD rats Divided into 7 groups: blank control group, sham operation group, model group (5 ng CCL2), memantine group (10 mg/kg•d-1), low TanA (25 mg/kg•d-1), medium ( 50 mg/kg•d-1), high (75 mg/kg•d-1) dose groups, 8 in each group. Except for the blank control group, the other groups were injected bilateral hippocampus with corresponding drugs [2]. After modeling, the Morris water maze was used to detect the learning and memory ability of rats, hematoxylin-eosin (HE) staining was used to observe the morphology of hippocampal neurons, and to detect superoxide dismutase (SOD) and glutathione in the hippocampus. The activity of oxidase (GSH-Px) and the content of malondialdehyde (MDA), the relative expression of caspase-3, caspase-8, and caspase-9 mRNA were determined by real-time fluorescent quantitative PCR (qPCR) method. The results showed that TanA can reduce the cognitive function and learning and memory impairment caused by CCL2 on the hippocampus of rats, and improve the cognitive function of rats. The mechanism is related to antioxidant and inhibition of nerve cell apoptosis.
In conclusion, the study found that CCl2 can induce the occurrence of inflammatory response and excitatory toxicity in the hippocampus, and eventually promote the apoptosis of hippocampus cells, and injure the learning and memory ability of rats.Based on the study of the central pathogenic mechanism of CCL2, it is important to find some potential drugs against CCL2 for the development of neuroprotective drugs and drugs to improve learning and cognitive ability.
[1] Naringin improves learning and memory impairment caused by CCL2 in rats and its mechanism [J].
[2] Study on the improvement effect of tanshinone A on rat cognitive dysfunction induced by CC chemokine ligand 2 and its mechanism [J].