http://www.sciencedirect.com/science/article/pii/S0028390813005030
- a Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, 127th Changle West Road, Xi'an 710032, China
- b Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
- c Department of Psychosomatic Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
Open Access
Highlights
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- rhTrx-1 ameliorated spatial learning and memory deficits induced by ischemia.
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- rhTrx-1 promoted ischemia-induced neurogenesis in DG.
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- rhTrx-1 enhanced proliferation and neuronal differentiation of cultured NSCs.
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- Neurogenesis enhanced by rhTrx-1 was inhibited by U0126 – inhibitor of ERK signaling pathway.
Abstract
Cerebral
ischemia (CI) can induce loss of hippocampal neurons, causing cognitive
dysfunction such as learning and memory deficits. In adult mammals, the
hippocampal dentate gyrus contains neural stem cells (NSCs) that
continuously generate newborn neurons and integrate into the
pre-existing networks throughout life, which may ameliorate cognitive
dysfunction following CI. Recent studies have demonstrated that
recombinant human thioredoxin-1 (rhTrx-1) could promote proliferation of
human adipose tissue-derived mesenchymal stem cells and angiogenesis.
To investigate whether rhTrx-1 also regulates hippocampal neurogenesis
following CI and its underlying mechanisms, adult mice were subjected to
bilateral common carotid arteries occlusion (BCCAO) to induce CI and
treated with rhTrx-1 before reperfusion. Mice treated with rhTrx-1
showed shortened escape latencies in Morris water maze by 30 days and
improvements in spatial memory demonstrated by probe trial test.
Enhanced NSCs proliferation was observed at day 14, indicated by BrdU
and Ki67 immunostaining. Doublecortin (DCX)+ cells were also significantly increased following rhTrx-1 treatment. Despite increases in BrdU+/NeuN+ cells by day 30, the double-labeling to total BrdU+
ratio was not affected by rhTrx-1 treatment. The promotive effects of
rhTrx-1 on NSCs proliferation and differentiation were further confirmed
in in vitro assays. Western blot revealed increased ERK1/2
phosphorylation after rhTrx-1 treatment, and the ERK inhibitor U0126
abrogated the effects of rhTrx-1 on NSCs proliferation. These results
provide initial evidence that rhTrx-1 effects neurogenesis through the
ERK signaling pathway and are beneficial for improving spatial learning
and memory in adult mice following global CI.
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