Hypoxic–hyperoxic conditioning and dementia

Mallet, Robert T.; Burtscher, Johannes; Манухина, Е. Б.; Downey, H. Fred; Глазачев, О. С.; Serebrovskaya, Tatiana V.; Burtscher, Martin

doi:10.1016/b978-0-12-815854-8.00047-1

Cited by 18 publications

(37 citation statements)

References 51 publications

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“…Hypoxic conditioning benefits mitochondria by ameliorating cellular environments; besides enhancing mitochondrial functioning, it boosts cellular oxidative defenses, oxygen and glucose supply and reduces inflammation [ 173 ]. Related approaches represent promising novel treatment strategies in diseases of the central nervous system [ 214 ] and in particular for neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…As outlined above, the pharmacological modulation of pathways involved in hypoxia adaptation, including HIFs, the sphingosine system, δ-opioid receptors and NMDARs, represents a promising approach against neurodegeneration. Conditioning approaches can be applied to strengthen mitochondrial functions, increase the endogenous oxidative stress defense and reduce neuroinflammation [ 173 ], processes that are all central in HD pathogenesis (see below). Such strategies are able to improve brain tissue resilience and thus brain cell health, which has been suggested to be an important feature of future neurodegeneration treatment strategies with greater translational potential than previous strategies developed in pre-clinical models [ 174 ].…”

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

“…One of the main benefits of hypoxic conditioning is the improvement of mitochondrial integrity and function that is thought to be at the core of conditioning-mediated neuroprotection [ 34 , 173 , 178 ]. A reduced supply of oxygen results in the HIF-mediated upregulation of mitophagy and decreases in mitochondrial mass and metabolism [ 178 ], as well as in a net downregulation of mitochondrial respiration [ 56 ].…”

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

“…As major ROS producers, mitochondria are intimately linked to oxidative stress. ROS are also important regulators of cellular adaptations to hypoxia [ 55 ] and hypoxic conditioning in turn can induce an upregulation of the antioxidative defense capacity [ 173 , 198 ] and may therefore be protective in HD pathogenesis. A recent study in human renal cell and neuroblastoma-derived cell lines demonstrated the protection from toxins (lidocaine in this study) conferred by HIF-1 [ 199 ].…”

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

“…While hypoxia is a potent inducer of inflammation [ 202 ], hypoxic conditioning has anti-inflammatory effects [ 173 ] and leads to beneficial adaptations of the innate immune system [ 203 ]. Therefore, the benefits of hypoxic conditioning with regard to neuroinflammation likely rely on conditioning’s general neuroprotective potential, but also on the involvement of associated signaling pathways in immune system functions like, for example, that of HIF-1 [ 102 ].…”

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

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A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Burtscher

Maglione

Pardo

et al. 2021

IJMS

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Neurodegenerative diseases are characterized by adverse cellular environments and pathological alterations causing neurodegeneration in distinct brain regions. This development is triggered or facilitated by conditions such as hypoxia, ischemia or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Targeting intracellular downstream consequences to specifically reverse these pathological changes proved difficult to translate to clinical settings. Here, we discuss the potential of more holistic approaches with the purpose to re-establish a healthy cellular environment and to promote cellular resilience. We review the involvement of important molecular pathways (e.g., the sphingosine, δ-opioid receptor or N-Methyl-D-aspartate (NMDA) receptor pathways) in neuroprotective hypoxic conditioning effects and how these pathways can be targeted for chemical conditioning. Despite the present scarcity of knowledge on the efficacy of such approaches in neurodegeneration, the specific characteristics of Huntington’s disease may make it particularly amenable for such conditioning techniques. Not only do classical features of neurodegenerative diseases like mitochondrial dysfunction, oxidative stress and inflammation support this assumption, but also specific Huntington’s disease characteristics: a relatively young age of neurodegeneration, molecular overlap of related pathologies with hypoxic adaptations and sensitivity to brain hypoxia. The aim of this review is to discuss several molecular pathways in relation to hypoxic adaptations that have potential as drug targets in neurodegenerative diseases. We will extract the relevance for Huntington’s disease from this knowledge base.

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Section: Discussionmentioning

confidence: 99%

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

Section: Conditioning Benefits On Mitochondrial Dysfunctions Oxidmentioning

confidence: 99%

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A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Burtscher

Maglione

Pardo

et al. 2021

IJMS

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Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment

Belmonte

Holmgren

Wills

et al. 2022

Alzheimer's & Dementia

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Introduction Epigenetic stimuli induce beneficial or detrimental changes in gene expression, and consequently, phenotype. Some of these phenotypes can manifest across the lifespan—and even in subsequent generations. Here, we used a mouse model of vascular cognitive impairment and dementia (VCID) to determine whether epigenetically induced resilience to specific dementia‐related phenotypes is heritable by first‐generation progeny. Methods Our systemic epigenetic therapy consisted of 2 months of repetitive hypoxic “conditioning” (RHC) prior to chronic cerebral hypoperfusion in adult C57BL/6J mice. Resultant changes in object recognition memory and hippocampal long‐term potentiation (LTP) were assessed 3 and 4 months later, respectively. Results Hypoperfusion‐induced memory/plasticity deficits were abrogated by RHC. Moreover, similarly robust dementia resilience was documented in untreated cerebral hypoperfused animals derived from RHC‐treated parents. Conclusions Our results in experimental VCID underscore the efficacy of epigenetics‐based treatments to prevent memory loss, and demonstrate for the first time the heritability of an induced resilience to dementia.

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Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?

et al. 2021

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Several lines of research point to a key role of low oxygen supply (hypoxia) in Parkinson's disease pathogenesis. Although severe hypoxia is detrimental for the brain, physiological adaptations to mild hypoxia are neuroprotective. Herein we discuss, how neuroprotective effects can be induced by hypoxia conditioning and how related approaches have the potential to be harnessed as therapeutic strategies in Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society

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Hypoxic–hyperoxic conditioning and dementia

Cited by 18 publications

References 51 publications

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment

Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?

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