Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin-like growth factor-1 signalling.

Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin-like growth factor-1 signalling.
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DOI:
10.1111/nan.12146
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发表时间:
2015-06
影响因子:
5
通讯作者:
Briones TL
Briones TL
中科院分区:
医学2区
文献类型:
--
作者:
Wadowska M;Woods J;Rogozinska M;Briones TL

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使用丰富的环境(EE)住房已被证明可以促进脑缺血性损伤的恢复,但其有益作用的潜在机制仍不清楚。在这里,我们检查了EE住房对缺血诱导的神经退行性变和认知障碍的有益影响是否与海马中胰岛素样生长因子-1(IGF-1)信号传导增加有关。研究纳入了42只成年雄性Wistar大鼠,并接受了缺血或假手术。将每组大鼠进一步随机分配至EE或标准实验室笼舍(对照)。大鼠从麻醉中恢复后立即置于指定的饲养条件下。缺血后2周进行线索学习和辨别学习任务的行为测试。在行为测试后对大鼠实施安乐死,并分析海马的IGF-1水平、IGF-1受体(IGF-1 R)活化、蛋白激酶B(Akt)通路活化、神经元丢失和半胱天冬酶3表达。我们的数据表明,EE住房:(1)减轻缺血诱导的神经元损失;(2)减弱缺血诱导的海马中caspase 3免疫反应性增加;(3)改善缺血诱导的认知障碍;(4)增加IGF-1 R激活和缺血损伤后通过Akt途径的信号传导。最终,这些发现表明IGF-1信号传导可能是EE在优化脑缺血损伤后恢复方面的有益作用的潜在机制之一。
Use of enriched environment (EE) housing has been shown to promote recovery from cerebral ischaemic injury but the underlying mechanisms of their beneficial effects remains unclear. Here we examined whether the beneficial effects of EE housing on ischaemia‐induced neurodegeneration and cognitive impairment are associated with increased insulin‐like growth factor‐1 (IGF‐1) signalling in the hippocampus. Forty‐two adult male Wistar rats were included in the study and received either ischaemia or sham surgery. Rats in each group were further randomized to either: EE or standard laboratory cage housing (control). Rats were placed in their assigned housing condition immediately after recovery from anaesthesia. Behavioural testing in the cued learning and discrimination learning tasks were conducted 2 weeks after ischaemia. Rats were euthanized after behavioural testing and the hippocampus was analysed for IGF‐1 level, IGF‐1 receptor (IGF‐1R) activation, protein kinase B (Akt) pathway activation, neurone loss and caspase 3 expression. Our data showed that EE housing: (1) mitigated ischaemia‐induced neuronal loss; (2) attenuated ischaemia‐induced increase in caspase 3 immunoreactivity in the hippocampus; (3) ameliorated ischaemia‐induced cognitive impairments; and (4) increased IGF‐1R activation and signalling through the Akt pathway after ischaemic injury. Ultimately, these findings suggest the possibility that IGF‐1 signalling may be one of the underlying mechanisms involved in the beneficial effects of EE in optimizing recovery following cerebral ischaemic injury.
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