Metabolic regulatory clues from the naked mole rat: Toward brain regulatory functions during stroke

Nathaniel, Thomas I.; Otukonyong, Effiong; Okon, Marvin; Chaves, J. M.; Cochran, Thomas; Nathaniel, Adebobola I.

doi:10.1016/j.brainresbull.2013.07.008

Cited by 12 publications

(11 citation statements)

References 123 publications

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“…This low basal metabolic rate of NMR is marginally depressed further during experimental hypoxia (3% O 2 ), while T b in normoxic and hypoxic animals was maintained at ~28 °C (Nathaniel et al . ).…”

Section: Hypometabolism Translatedmentioning

confidence: 97%

“…Not surprisingly, the stress resilience of the NMR extends to its neurons (reviewed: Nathaniel et al . , Larson et al . ).…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

“…It is currently discussed whether NMR's robust hypoxia tolerance is actually based on traits acquired through the species’ retention of juvenile characteristics into adulthood (neoteny hypothesis; Nathaniel et al . , Larson et al . ).…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

“…0.27 mL O 2 g −1 h −1 ; Buffenstein & Yahav , Nathaniel et al . ) compared to a mouse (i.e. 1.65 mL O 2 g −1 h −1 ; Schmidt‐Nielsen ).…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

“…Of particular interest in this regard could be the exploration of ‘pharmacological means to induce metabolic suppression in non‐hypoxia tolerating species’ (Nathaniel et al . ; see Organ protection and metabolic depression by hydrogen sulfide and other gases). More advanced to date, however, is the clinical application of therapeutic hypothermia as neuro‐ and cardioprotective measure against I‐R‐related brain and heart injuries (Yenari et al .…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

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Hypometabolism as the ultimate defence in stress response: how the comparative approach helps understanding of medically relevant questions

Gorr

2016

Acta Physiologica

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First conceptualized from breath-hold diving mammals, later recognized as the ultimate cell autonomous survival strategy in anoxia-tolerant vertebrates and burrowing or hibernating rodents, hypometabolism is typically recruited by resilient organisms to withstand and recover from otherwise life-threatening hazards. Through the coordinated down-regulation of biosynthetic, proliferative and electrogenic expenditures at times when little ATP can be generated, a metabolism turned 'down to the pilot light' allows the re-balancing of energy demand with supply at a greatly suppressed level in response to noxious exogenous stimuli or seasonal endogenous cues. A unifying hallmark of stress-tolerant organisms, the adaptation effectively prevents lethal depletion of ATP, thus delineating a marked contrast with susceptible species. Along with disengaged macromolecular syntheses, attenuated transmembrane ion shuttling and PO -conforming respiration rates, the metabolic slowdown in tolerant species usually culminates in a non-cycling, quiescent phenotype. However, such a reprogramming also occurs in leading human pathophysiologies. Ranging from microbial infections through ischaemia-driven infarcts to solid malignancies, cells involved in these disorders may again invoke hypometabolism to endure conditions non-permissive for growth. At the same time, their reduced activities underlie the frequent development of a general resistance to therapeutic interventions. On the other hand, a controlled induction of hypometabolic and/or hypothermic states by pharmacological means has recently stimulated intense research aimed at improved organ preservation and patient survival in situations requiring acutely administered critical care. The current review article therefore presents an up-to-date survey of concepts and applications of a coordinated and reversibly down-regulated metabolic rate as the ultimate defence in stress responses.

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Section: Hypometabolism Translatedmentioning

confidence: 97%

“…Not surprisingly, the stress resilience of the NMR extends to its neurons (reviewed: Nathaniel et al . , Larson et al . ).…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

Section: Hypometabolism Translatedmentioning

confidence: 99%

“…0.27 mL O 2 g −1 h −1 ; Buffenstein & Yahav , Nathaniel et al . ) compared to a mouse (i.e. 1.65 mL O 2 g −1 h −1 ; Schmidt‐Nielsen ).…”

Section: Hypometabolism Translatedmentioning

confidence: 99%

Section: Hypometabolism Translatedmentioning

confidence: 99%

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Hypometabolism as the ultimate defence in stress response: how the comparative approach helps understanding of medically relevant questions

Gorr

2016

Acta Physiologica

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Oxidative damage and amyloid‐β metabolism in brain regions of the longest‐lived rodents

Edrey

Oddo

Cornelius

et al. 2013

J of Neuroscience Research

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Naked mole rats (NMRs) are the longest-lived rodents, with young individuals having high levels of Aβ in their brains. The purpose of this study was twofold: to assess the distribution of Aβ in key regions of NMR brains (cortex, hippocampus, cerebellum) and to understand whether the accumulation of Aβ is due to enhanced production or decreased degradation. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotective proteins, such as heat shock proteins (Hsps), which play a central role in the cellular mechanisms of stress tolerance. Amyloid precursor protein processing, lipid peroxidation, Hsps, redox status, and protein degradation processes were therefore assessed in key NMR brain regions. NMR brains had high levels of lipid peroxidation compared with mice, and the NMR hippocampus had the highest levels of the most toxic moiety of Aβ (soluble Aβ1–42). This was due not to increased Aβ production but rather to low antioxidant potential, which was associated with low induction of Hsp70 and heme oxygenase-1 as well as low ubiquitin-proteasome activity. NMRs may therefore serve as natural models for understanding the relationship between oxidative stress and Aβ levels and its effects on the brain.

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Targeting Acid-Sensing Ion Channels in Disease

Senescall,

Budusan,

Knezic

et al. 2024

Ion Channels as Targets in Drug Discovery

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Metabolic regulatory clues from the naked mole rat: Toward brain regulatory functions during stroke

Cited by 12 publications

References 123 publications

Hypometabolism as the ultimate defence in stress response: how the comparative approach helps understanding of medically relevant questions

Hypometabolism as the ultimate defence in stress response: how the comparative approach helps understanding of medically relevant questions

Oxidative damage and amyloid‐β metabolism in brain regions of the longest‐lived rodents

Targeting Acid-Sensing Ion Channels in Disease

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