Study The Effects Of Seed Oil From Lycium Barbarum L. On Depression-like Behavior And Cognitive Deficits In Chronically Stressed Mice

Objective: To investigating the neuroprotective effects of Lycium barbarum seed oil(LBSO) in against the depressant-like behavior and concomitant cognitive dysfunction, and changes in hippocampal BDNF signaling pathway in chronically stressed mice.Methods: The mouse model of chronic unpredictable stress(CUS) was employed in this study. 90 adult male ICR mice were divided randomly into 6 groups(15 in each group) including Normal control group, Vehicle group(CUS model group), Fluoxetine group(positive control group) and three LBSO groups at the dosage of 2.5 m L/kg, 5 m L/kg and 10 m L/kg. Except to Normal control group, each groups repeated drug treatment was performed once daily, for 35 days. Except to the Animals of Normal control group, the other Animals were subjected to different unpredictable stressors for a period of 28 day, these stressors including food and water deprivation(24 h), night lighting(12h), damp sawdust, noise stimulation(15 min), cold water swimming(4�C for 5 min), sandwiched tail(1 min), foot electric shock(30 V, 0.5 Hz for 5 min) and placed in tethering device(1h). Behavior tests like open field test(OFT), forced swim test(FST), tail suspension test(TST) and Morris water maze test(MWMT) were performed after CUS. During the behavior tests, the CUS mice still suffered the stimulation and drug treatment. After the behavioral test is completed with 4% chloral hydrate anesthetized mice until the corneal reflex loss get blood form orbital plexus,centrifugation to get serum. 10 mice of each group craniotomy to get hippocampus, other mice was perfusion saline and followed 4% paraformaldehyde into heart, then craniotomy to get whole brain. The whole brains were employed paraffin-embedded and thin sections. The morphological changes of pyramidal neurons in the hippocampus were studied by HE staining and Nissl staining. Serum corticosterone level was assessed by Elisa kit. Protein expression level of BDNF, p-CREB and p-CREB/CREB in hippocampus were assessed by Western blot assays and immunohistochemistry approaches.Results: The chronic unpredictable stress(CUS) could induce behavioral alterations, including decreasing the ambulation in OFT(p<0.01, vs Normal), increasing the immobility time in FST(p<0.01, vs Normal) and TST(p<0.05, vs Normal). LBSO can reverse this behavioral alterations by increasing the ambulation in OFT(LBSO 10 m L/kg, p<0.01), reducing the immobility time in FST(LBSO 10 m L/kg, p<0.01) and TST(LBSO 10 m L/kg, p<0.01). The CUS could induce cognitive deficits at learning performance(p<0.05, vs Normal) and memory capacity(p<0.01, vs Normal) in MWMT. Whereas LBSO can improve the learning performance of mice in the learning procedure of MWMT(LBSO 10 m L/kg, p<0.01), and may improve the Memory capacity of mice in the Probe Trials of MWMT(LBSO 10 m L/kg, p<0.05, p>0.05, p<0.01). The CUS could induce serum corticosterone level soaring(p<0.01, vs Normal) and neuron loss in the hippocampus(p<0.05, vs Normal).LBSO treatment can reduce serum corticosterone level(LBSO 10 m L/kg, p<0.05) along with preventing the neuron loss(LBSO 10 m L/kg, p<0.05) in the hippocampus. The CUS could downregulate the CREB-BDNF signaling pathway(p-CREB/CREB, p<0.05, in Western blot, p<0.01 in immunohistochemistry, vs Normal)(BDNF, p<0.05, in Western blot, p<0.01 in immunohistochemistry vs Normal). LBSO can upregulate BDNF expression(LBSO 10 m L/kg, p<0.01) and phosphorylation of CREB(LBSO 10 m L/kg, p<0.01 in immunohistochemistry, p<0.05 in Western blot) in hippocampus during the CUS procedure.Conclusion: Lycium barbarum seed oil has a significant effect in alleviation the CUS-induced depressive-like behaviors and cognitive deficits through maintaining the BDNF signaling pathway in hippocampus.