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Abstract
Purpose: To investigate the neuroprotective effects of Lycium barbarum polysaccharide (LBP) against concomitant cognitive dysfunction and changes in hippocampal CREB-BDNF signaling pathway in chronically unpredictable stressed mice.Methods: The mice were subjected to different unpredictable stressors for a period of 4 weeks. Behavioral tests, including open field (OFT) and Morris water maze (MWMT) tests were used to evaluate pharmacological effects. Serum corticosterone levels, protein expression level of BDNF and pCREB/CREB in hippocampus were assessed by ELISA, Western blot and immunohistochemistry methods, respectively. Morphological changes in pyramidal neurons in the hippocampus were studied by Nissl staining.Results: LBP improved mice performance in MWMT, indicating that it reversed chronic unpredictable stress (CUS)-induced cognitive deficits. LBP treatment reduced serum corticosterone levels and prevented neuron loss in the hippocampus. It maintained expression levels of BDNF and phosphorylation of CREB in hippocampus during CUS procedure.Conclusion: Lycium barbarum polysaccharide protects CREB-BDNF signaling pathway in hippocampus and relieves CUS-induced cognitive deficits. These results suggest that Lycium barbarum polysaccharides is potentially an alternative neuro-protective agent against stress-induced psychopathological dysfunction.Keywords: Lycium barbarum, Polysaccharide, Chronic unpredictable stress, Cognitive deficits, Brainderived neurotrophic factor, Calcium/cyclic-AMP responsive binding protein
Highlights
IntroductionLycium barbarum (wolfberries, Solanaceae) is used in traditional Chinese medicine for treating diminished visual acuity, dry cough, abdominal pain, headache, infertility, and fatigue [1]
Lycium barbarum is used in traditional Chinese medicine for treating diminished visual acuity, dry cough, abdominal pain, headache, infertility, and fatigue [1]
Lycium barbarum polysaccharide (LBP) reversed the memory damage induced by chronic unpredictable stress (CUS) at a dose of 400 mg/kg by significantly increasing the percentage of distance traveled in target quarter (n = 8, p < 0.01 vs. vehicle); and the percentage of time in target quarter (n = 8, p < 0.01, vs. vehicle). These results demonstrate LBP restored CUS-induced spatial learning and memory damage, and suggest that the cognitive deficit induced by CUS could be reversed by LBP treatment
Summary
Lycium barbarum (wolfberries, Solanaceae) is used in traditional Chinese medicine for treating diminished visual acuity, dry cough, abdominal pain, headache, infertility, and fatigue [1]. Many pharmacological effects of LBP have been reported. LBP has hypoglycemic and hypolipidemic effects, and it could be used for treating type 2 diabetes [2] and cancer [3]. LBP improves sexual behavior and increases neurogenesis [4], as well as Alzheimer’s disease CREB-BDNF signaling pathway in hippocampus (AD), colitis, fatigue, glaucoma and stroke [5]. Chronic unpredictable stress (CUS), which is one of the extensive used rodent models in stress related mental disorders such as anxiety and depression [8]. Exposure to CUS has been shown to induce cognitive deficits [7], reduce neurotrophic factors, increase corticosterone levels and even decrease the number of neurons and glia in hippocampus and other cerebral regions [6]
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