Neurogenesis in the adult rat brain after intermittent hypoxia

Zhu, Lijing; Zhao, Tong; Li, Haisheng; Zhao, Huiqing; Wu, Liying; An-wei, Ding; Fan, Wenhong; Fan, Ming

doi:10.1016/j.brainres.2005.04.075

Cited by 90 publications

(70 citation statements)

References 21 publications

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“…The number of BrdU ϩ cells was increased by IH mimicking altitude of 3000 and 5000 m (F (2,15) ϭ 16.628, p Ͻ 0.001; post hoc analysis, p Ͻ 0.01 5000 m vs control), although the increase at 3000 m was not statistically significant ( p ϭ 0.056 vs control). In general agreement with a previous report (Zhu et al, 2005), which demonstrates that the number of BrdU ϩ cells was increased in both the DG and subventricular zone by 14 d IH mimicking 3000 and 5000 m in altitudes, these results suggest that IH promotes the proliferation of NPCs in adult hippocampus. Unless otherwise indicated, IH in this paper indicates IH mimicking 5000 m in altitude.…”

Section: Ih Enhances Neurogenesis In Adult Hippocampussupporting

confidence: 93%

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Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

Zhu¹,

Yan²,

Zhang³

et al. 2010

J. Neurosci.

195

137

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Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressantlike effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.

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Section: Ih Enhances Neurogenesis In Adult Hippocampussupporting

confidence: 93%

“…Recently, it has been shown that hypoxia promoted neurogenesis in vitro (Shingo et al, 2001;Jin et al, 2002) and enhanced the proliferation of neuroprogenitor cells (NPCs) in vivo (Zhu et al, 2005). In this context, we investigated the in vivo effects of IH on hippocampal neurogenesis and its potential AD effects.…”

Section: Introductionmentioning

confidence: 98%

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

Zhu¹,

Yan²,

Zhang³

et al. 2010

J. Neurosci.

195

137

View full text Add to dashboard Cite

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“…Furthermore, previous studies have confirmed that fiber connections between bilateral visual fields undergo rapid and exuberant sprouting and pruning to facilitate topographic reorganization in recovery from central nerve system damage (Gilbert and Li 2012), and specific neurons in the adult brain also carry a latent neurogenic program even after hypoxic exposure (Zhu et al. 2005). In the setting of an adult brain in adaptation to long lasting inspiratory hypoxia, which of the above mentioned events triggers or dominates the DTI‐derived fiber changes needs to be further identified.…”

Section: Discussionmentioning

confidence: 99%

Long‐term acclimatization to high‐altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain

Chen

Li²,

Han³

et al. 2016

Brain and Behavior

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BackgroundStructural and functional networks can be reorganized to adjust to environmental pressures and physiologic changes in the adult brain, but such processes remain unclear in prolonged adaptation to high‐altitude (HA) hypoxia. This study aimed to characterize the interhemispheric functionally and structurally coupled modifications in the brains of adult HA immigrants.MethodsWe performed resting‐state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 16 adults who had immigrated to the Qinghai‐Tibet Plateau (2300–4400 m) for 2 years and in 16 age‐matched sea‐level (SL) controls. A recently validated approach of voxel‐mirrored homotopic connectivity (VMHC) was employed to examine the interhemispheric resting‐state functional connectivity. Areas showing changed VMHC in HA immigrants were selected as regions of interest for follow‐up DTI tractography analysis. The fiber parameters of fractional anisotropy and fiber length were obtained. Cognitive and physiological assessments were made and correlated with the resulting image metrics.ResultsCompared with SL controls, VMHC in the bilateral visual cortex was significantly increased in HA immigrants. The mean VMHC value extracted within the visual cortex was positively correlated with hemoglobin concentration. Moreover, the path length of the commissural fibers connecting homotopic visual areas was increased in HA immigrants, covarying positively with VMHC.ConclusionsThese observations are the first to demonstrate interhemispheric functional and structural connectivity resilience in the adult brain after prolonged HA acclimatization independent of inherited and developmental effects, and the coupled modifications in the bilateral visual cortex indicate important neural compensatory mechanisms underlying visual dysfunction in physiologically well‐acclimatized HA immigrants. The study of human central adaptation to extreme environments promotes the understanding of our brain's capacity for survival.

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“…19 We hypothesized that SVZ hypoxia may extend beyond the acute phase. Hypoxyprobe-1 was injected 6 weeks after 2 hours of MCAO or sham surgery and animals perfused 2 hours thereafter.…”

Section: Subventricular Zone Is Transiently Hypoxic After Mcaomentioning

confidence: 99%

“…This seems highly warranted because hypoxia stimulates angiogenesis 12 and proliferation and differentiation of neural progenitors in vitro 18 and in vivo. 19 The second objective was to explore whether MCAO causes changes in vascularization in SVZ and adjacent striatum, and whether these changes are attributable to angiogenesis. The third objective was to analyze the distribution of neuroblasts at various distances from blood vessels at different time points after MCAO.…”

mentioning

confidence: 99%

Long-Term Neuroblast Migration Along Blood Vessels in an Area With Transient Angiogenesis and Increased Vascularization After Stroke

Thored

Wood

Arvidsson

et al. 2007

Stroke

375

313

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Background and Purpose-Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature. Methods-Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5Ј-bromo-2Јdeoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy. Results-The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels. Conclusions-The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.

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Neurogenesis in the adult rat brain after intermittent hypoxia

Cited by 90 publications

References 21 publications

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

Long‐term acclimatization to high‐altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain

Long-Term Neuroblast Migration Along Blood Vessels in an Area With Transient Angiogenesis and Increased Vascularization After Stroke

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