Effects of hypoxic preconditioning on synaptic ultrastructure in mice

Liu, Yu; Sun, Zhanfang; Sun, Shiqun; Duan, Yunyun; Shi, Jingfei; Qi, Zhifeng; Meng, Ran; Sun, Yujie; Zeng, Xianwei; Chui, Dehua; Ji, Xunming

doi:10.1002/syn.21777

Cited by 4 publications

(2 citation statements)

References 20 publications

(24 reference statements)

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“…Additionally, it could parallel certain changes seen in other systems in response to HPC. For example, in the olfactory bulb, synaptic efficacy appears to be altered for a short period of time after HPC, possibly due to changes in synaptic ultrastructure (Liu et al, 2015). Also, HPC has been described as increasing glutamate receptors and nitric oxide in ways that may relate to its neuroprotective effects (Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Response to Hypoxic Preconditioning of Glial Cells from the Roof of the Fourth Ventricle

et al. 2020

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The cerebellum harbors a specialized area on the roof of the fourth ventricle that is composed of glial cells and neurons that interface with the cerebrospinal fluid. This region includes the so-called ventromedial cord (VMC), which is composed of cells that are glial fibrillary acidic protein (GFAP)-positive and nestin-positive and distributes along the midline in association with blood vessels. We hypothesized that these cells should compare to GFAP and nestin-positive cells that are known to exist in other areas of the brain, which undergo proliferation and differentiation under hypoxic conditions. Thus, we tested whether cells of the VMC would display a similar reaction to hypoxic preconditioning (HPC). Indeed, we found that the VMC does respond to HPC by reorganizing its cellular components before it gradually returns to its basal state after about a week. This response we documented by monitoring global changes in the expression of GFAP-EGFP in transgenic mice, using light-sheet fluorescence microscopy (LSFM) revealed a dramatic loss of EGFP upon HPC, and was paralleled by retraction of Bergmann glial cell processes. This EGFP loss was supported by western blot analysis, which also showed a loss in the astrocyte-markers GFAP and ALDH1L1. On the other hand, other cell-markers appeared to be upregulated in the blots (including nestin, NeuN, and Iba1). Finally, we found that HPC does not remarkably affect the incorporation of BrdU into cells on the cerebellum, but strongly augments BrdU incorporation into periventricular cells on the floor of the fourth ventricle over the adjacent medulla. This article is part of a Special Issue entitled: Honoring Ricardo Miledi -outstanding neuroscientist of XX-XXI centuries.

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Section: Discussionmentioning

confidence: 99%

Response to Hypoxic Preconditioning of Glial Cells from the Roof of the Fourth Ventricle

et al. 2020

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“…Whether used in traditional Chinese and Tibetan medicine or researched in experimental animal models, salidroside has shown the ability to protect the body or cells against hypoxia; however, the underlying mechanism of action against simulated and hypoxia conditions is unclear. On this basis, we speculate that with respect to antihypoxia, salidroside may be comparable to HPC, by maintaining the integrity of the mitochondria [4,10,11]. Therefore, in this study, we aim to explore the antihypoxia mechanism of salidroside compared with HPC in PC12 cells and also expect to provide experimental data for its further clinical application.…”

Section: Introductionmentioning

confidence: 99%

Comparative Study on the Protective Effects of Salidroside and Hypoxic Preconditioning for Attenuating Anoxia-Induced Apoptosis in Pheochromocytoma (PC12) Cells

Zhang

et al. 2016

Med Sci Monit

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BackgroundHypoxia is an important sign that can result from body injuries or a special condition such as being at a high altitude or deep water diving. In the current studies, hypoxic preconditioning (HPC) plays a key role in reducing hypoxia-induced apoptosis. We aimed to study the pharmacologic preconditioning effects of salidroside versus those of HPC in hypoxia-/anoxia-induced apoptosis in PC12 cells (pheochromocytoma).Material/MethodsPC12 cells were treated by different experimental conditions: control condition, hypoxia condition, HPC condition, low-/middle-/high-dose condition of salidroside, cyclosporine A (CsA), and oratractyloside (ATR). The cell viability, lactate dehydrogenase (LDH) activity, apoptosis, mitochondrial membrane potential (MMP), intracellular Ca2+, caspase-3 activity, and expression of Bcl-2 were detected in PC12 cells after the hypoxia treatment. Salidroside, extracted from the traditional Chinese herb Rhodiola rosea L, plays an essential role in reducing hypoxia-induced apoptosis in PC12 cells by the mitochondrial pathway.ResultsSalidroside decreased the apoptosis and increased the viability of hypoxia-induced PC12 cells more effectively than HPC Moreover, salidroside markedly stabilized MMP and intracellular Ca2+, reduced or inhibited LDH and caspase-3 activity, and up-regulated Bcl-2; CsA and ATR showed corresponding function.ConclusionsSalidroside administration restrains apoptosis induced by hypoxia in PC12 cells. The protective effects are mediated by preservation of mitochondrial integrity and MMP to inhibit the excessive Ca2+ influx and caspase-3 activity and to promote the Bcl-2 expression, providing a potential clinical and effective therapeutic mechanism to reduce deaths from ischemic or hypoxic injury.

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Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease

Correia

Machado

Alves

et al. 2021

IJMS

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The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

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Effects of hypoxic preconditioning on synaptic ultrastructure in mice

Cited by 4 publications

References 20 publications

Response to Hypoxic Preconditioning of Glial Cells from the Roof of the Fourth Ventricle

Response to Hypoxic Preconditioning of Glial Cells from the Roof of the Fourth Ventricle

Comparative Study on the Protective Effects of Salidroside and Hypoxic Preconditioning for Attenuating Anoxia-Induced Apoptosis in Pheochromocytoma (PC12) Cells

Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease

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