Article Text
Abstract
Introduction Cerebral ischaemia-induced depression is among the most frequent neuropsychiatric consequences and adversely impact the prognosis and recovery of patients. Although several brain regions have been implied in the development of ischaemia-induced depression, the brain region-specific neural cell apoptosis pathways have not been clarified yet.
Methods In this study, bilateral internal carotid artery occlusion (BICAO) mouse model was established to induce cerebral ischaemia. Sucrose preference, tail suspension and forced swim tests were conducted on mice at 7, 21 and 30 days after BICAO treatment. In addition, brain regional ischaemic neuron loss was investigated by using immunofluorescent staining of neuronal nuclei (NeuN) and caspase-8/-9-dependent cell apoptosis was also examined by western blot analysis.
Results BICAO-induced cerebral ischaemia resulted in decreased sucrose preference and increased immobility times, which were representative depressive-like behaviours of mice until 30 days after BICAO treatment compared with Sham-operated mice. This outcome was associated with significant neuron loss by using immunofluorescent staining and increased cleavage levels of pro-caspase-3/-8/-9, but not pro-caspase-12, by western blot analysis in hypothalamus, midbrain, prefrontal cortex and hippocampus of mice.
Conclusions This study showed that BICAO-induced ischaemia caused depressive-like behaviours and caspase-8/-9-dependent neural cell apoptosis in several brain regions, including hypothalamus and midbrain of mice.
- depression
- apoptosis
- bilateral internal carotid artery occlusion
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Footnotes
Contributors All the listed authors have participated actively in the study and approved the submitted manuscript. SL and JL: responsible for integrity of the entire study, study concepts and approved the final version of the manuscript to be published. SH and QD: data acquisition and analysis. SL: conducted the experimental studies and drafted the manuscript.
Funding This work was supported by grants from the Seed Grant of International Alliance of Translational Neuroscience (PXM-2014-014226-000006), Beijing Natural Science Foundation (7132070 and 7141001) and National Natural Science Foundation of China (81771414, 81301015, 31471142 and 31671205).
Competing interests None declared.
Ethics approval The Animal Care and Use Committee of Capital Medical University approved all experimental procedures of this study, which is in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Provenance and peer review Not commissioned; externally peer reviewed.