Aim To investigate whether Kv7 channels opener retigabine could alleviate memory impairment induced by chronic restraint stress （CRS） and the underlying neuroprotective mechanisms. Methods Adult male Kunming （KM） ...Aim To investigate whether Kv7 channels opener retigabine could alleviate memory impairment induced by chronic restraint stress （CRS） and the underlying neuroprotective mechanisms. Methods Adult male Kunming （KM） mice, weighing 20 - 25 g, were restrained in well-ventilated Plexiglass tubes for 6 h daily beginning from 10 ： 00 to 16 ： 00 for 21 consecutive days. Mice were injected with retigabine （ 10 mg · kg^-1） or vehicle （ 10% DM- SO） 30 rain before restraint stress for 21 days. After stressor cessation, the spatial learning and memory was deter- mined by Morris water maze test, the levels of p-Akt, p-GSK-3β and p-Erkl/2 of hippocampal tissues were exam- ined by western blot. Results Compared with control group, CRS mice exhibited significantly longer escape laten- cies on day 2, 3 and 4 （P 〈 0.05, P 〈 0. 01, P 〈 0.01 ） respectively, but retigabine （ 10 mg · kg^-1） treatment had no influences on escape latencies compared with CRS group. During the probe test, CRS mice spent significant less time in target quadrant than control group （P 〈 0.01 ）. Compared with CRS group, retigabine （ 10 mg · kg^-1 ） treatment increased the time spent in target quadrant （P 〈 0.01 ）. Additionally, the swimming speed showed no significant differences among groups. Western blot results showed that the levels of p-Akt, p-GSK-3β and p-Erkl/ 2 in the hippocampus of CRS mice were significantly decreased compared with control group. Compared with CRS group, retigabine （ 10 mg· kg^-1） treatment strongly prevented the reduction of p-Akt and p-GSK-3 β （P 〈 0.01 ）, but had no effect on the reduction of p-Erkl/2. Conclusion Retigabine protected against CRS-induced spatial memory retrieval impairment partly via activation of Akt/GSK-3β signaling pathway.展开更多
BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely use...BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.展开更多
文摘Aim To investigate whether Kv7 channels opener retigabine could alleviate memory impairment induced by chronic restraint stress （CRS） and the underlying neuroprotective mechanisms. Methods Adult male Kunming （KM） mice, weighing 20 - 25 g, were restrained in well-ventilated Plexiglass tubes for 6 h daily beginning from 10 ： 00 to 16 ： 00 for 21 consecutive days. Mice were injected with retigabine （ 10 mg · kg^-1） or vehicle （ 10% DM- SO） 30 rain before restraint stress for 21 days. After stressor cessation, the spatial learning and memory was deter- mined by Morris water maze test, the levels of p-Akt, p-GSK-3β and p-Erkl/2 of hippocampal tissues were exam- ined by western blot. Results Compared with control group, CRS mice exhibited significantly longer escape laten- cies on day 2, 3 and 4 （P 〈 0.05, P 〈 0. 01, P 〈 0.01 ） respectively, but retigabine （ 10 mg · kg^-1） treatment had no influences on escape latencies compared with CRS group. During the probe test, CRS mice spent significant less time in target quadrant than control group （P 〈 0.01 ）. Compared with CRS group, retigabine （ 10 mg · kg^-1 ） treatment increased the time spent in target quadrant （P 〈 0.01 ）. Additionally, the swimming speed showed no significant differences among groups. Western blot results showed that the levels of p-Akt, p-GSK-3β and p-Erkl/ 2 in the hippocampus of CRS mice were significantly decreased compared with control group. Compared with CRS group, retigabine （ 10 mg· kg^-1） treatment strongly prevented the reduction of p-Akt and p-GSK-3 β （P 〈 0.01 ）, but had no effect on the reduction of p-Erkl/2. Conclusion Retigabine protected against CRS-induced spatial memory retrieval impairment partly via activation of Akt/GSK-3β signaling pathway.
基金Supported by National Natural Science Foundation of China,No.31501861Natural Science Foundation of Shandong Province,China,No.ZR2015CM013
文摘BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.
