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- W2998000547 abstract "Stroke is a major disease associated with high mortality and serious long-term disability. Usual treatments fail to improve long-term recovery and thrombolysis is only efficient on 10% of patients. Consequently, developing new treatments is necessary. The TREK-1 channel was shown to be protective against stroke. We have identified a peptide (spadin or PE 12-28) and its shortened analogs that are potent antidepressant and are able to inhibit TREK-1. Our aim was to demonstrate that these peptides have protective effects against post-stroke depression. For mimicking stroke on mice, we used the in vivo model of MCAO. Thanks to electrophysiology studies, we developed a protocol consisting in a two phase treatment, a low dose (0.03 mg/kg) for one week followed by a high dose (3 mg/kg) treatment for several weeks. At different time points, behavioral tests were performed in order measure both motor and cognitive performance of the animals. Treated mice showed a significant reduction of the immobility time in the Forced Swimming Test and in the latency to eat in the Novelty Suppressed Feeding test. Both tests demonstrate that the depressive state is improved. The learning capacity was increased in the Morris Water Maze and the motor coordination was improved in both rotarod and pole tests. Additionally, the increase in neurogenesis, measured by BrdU incorporation was still present even at 10 weeks post trauma. Taken together our results suggest that spadin and its analogs are very potent candidates for the development of new treatments improving stroke recovery, mainly by preventing the depression." @default.
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- W2998000547 date "2019-10-01" @default.
- W2998000547 modified "2023-09-25" @default.
- W2998000547 title "Spadin and shortened spadin analogs as efficient new antidepressants in mouse models of post-stroke depression" @default.
- W2998000547 doi "https://doi.org/10.1016/j.jns.2019.10.738" @default.
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