Mechanisms of cell survival in hypoxia and hypothermia

SUMMARYMost animals experience some degree of hypoxia and hypothermia during the course of their natural life history either as a consequence of ambient ‘exposure’ per se or through metabolic, respiratory and/or circulatory insufficiency. A prevailing experimental approach has been to probe tissues from natural models of hypoxia-tolerant and cold-tolerant vertebrates to look for common mechanisms of defence against O2 lack and hypothermia. The ability to sustain vital cellular functions in severe cases of either condition varies widely amongst the vertebrates. Like humans, the vast majority of mammals are unable to survive prolonged periods of hypothermia or O2 deprivation owing to irreversible membrane damage and loss of cellular ion homeostasis in vital organs such as the brain and heart. However, numerous hibernating endotherms, neonatal and diving mammals as well as many ectotherms can tolerate prolonged periods that would, in clinical terms, be called asphyxia or deep hypothermia. The key to their survival under such conditions lies in an inherent ability to downregulate their cellular metabolic rate to new hypometabolic steady states in a way that balances the ATP demand and ATP supply pathways.

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Deep hypothermia circulatory arrest: is it enough to protect the brain?

European Journal of Anaesthesiology ◽

10.1097/00003643-201406001-00329 ◽

2014 ◽

Vol 31 ◽

pp. 119

Author(s):

Y. Miyerbekov ◽

T. Kuandykov ◽

V. Mutagirov

Keyword(s):

Circulatory Arrest ◽

Deep Hypothermia ◽

The Brain

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The Biochemical Mechanisms of Salt Tolerance in Plants

10.5772/intechopen.101048 ◽

2021 ◽

Author(s):

Julio Armando Massange-Sánchez ◽

Carla Vanessa Sánchez-Hernández ◽

Rosalba Mireya Hernández-Herrera ◽

Paola Andrea Palmeros-Suárez

Keyword(s):

Salt Stress ◽

Crop Yields ◽

Membrane Damage ◽

Ion Homeostasis ◽

Antioxidant Compounds ◽

Plant Tolerance ◽

Ros Scavenging ◽

Dna Structures ◽

Biochemical Mechanisms ◽

Scavenging Enzymes

Salinity is one of the most severe environmental problems worldwide and affects plant growth, reproduction, and crop yields by inducing physiological and biochemical changes due to osmotic and ionic shifts in plant cells. One of the principal modifications caused by osmotic stress is the accumulation of reactive oxygen species (ROS), which cause membrane damage and alter proteins, DNA structures, and photosynthetic processes. In response, plants increase their arsenal of antioxidant compounds, such as ROS scavenging enzymes and nonenzymatic elements like ascorbate, glutathione, flavonoids, tocopherols, and carotenoids, and their rates of osmolyte synthesis to conserve ion homeostasis and manage salt stress. This chapter describes the principal biochemical mechanisms that are employed by plants to survive under salt-stress conditions, including the most recent research regarding plant tolerance, and suggests strategies to produce valuable crops that are able to deal with soil salinity.

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Remote control of neural function by X-ray-induced scintillation

10.1101/798702 ◽

2019 ◽

Cited By ~ 5

Author(s):

Takanori Matsubara ◽

Takayuki Yanagida ◽

Noriaki Kawaguchi ◽

Takashi Nakano ◽

Junichiro Yoshimoto ◽

...

Keyword(s):

Dopamine Neurons ◽

Neural Function ◽

X Rays ◽

Cellular Functions ◽

X Ray ◽

Functional Studies ◽

Clinical Dose ◽

Visible Luminescence ◽

Midbrain Dopamine ◽

The Brain

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), could effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles were non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level was sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables less invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.

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Experimental approach to overexpress pituitary adenylate cyclase activating polypeptide (PACAP) specifically in the hypothalamus

10.24124/2021/59163 ◽

2021 ◽

Author(s):

◽

Yamna Rahim

Keyword(s):

Energy Expenditure ◽

Experimental Approach ◽

Health Condition ◽

Specific Expression ◽

Steroidogenic Factor 1 ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Pituitary Adenylate Cyclase ◽

The Brain

Obesity is adetrimental health condition that occurs when energy intake, exceeds energy expenditure. Pituitary adenylatecyclase-activating polypeptide (PACAP) regulates energy expenditure, including adaptive thermogenesis, through the hypothalamic-sympatheticnervous system-brown adipose tissue axis. We hypothesize that PACAP expression in the ventromedial nucleus (VMN) is required for adaptive thermogenesis. To assess this, our goal is to develop an animal model that expresses PACAP specifically in the VMN of the hypothalamus. As a first step to achieving this goal, we established a protocol to deliver an adeno-associatedvirus (AAV) expressing the visible protein eGFP under the control of a VMN-specific promoter, steroidogenic factor 1 (SF1) using stereotaxic surgery. A second step was to develop a protocol to detect PACAP mRNA in the brain using in situ hybridization. Our results showed that the stereotaxic protocol was successful and provides significant progress towards achieving PACAP-specific expression in the VMN.

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Complex Activity and Short-term Memories in Reciprocally Connected Cerebral Organoids

10.1101/2021.02.16.431387 ◽

2021 ◽

Author(s):

Tatsuya Osaki ◽

Yoshiho Ikeuchi

Keyword(s):

Human Brain ◽

Three Dimensional ◽

Oscillatory Activity ◽

Cellular Functions ◽

Complex Activity ◽

Axonal Connections ◽

Brain Organoid ◽

External Stimuli ◽

The Brain

AbstractMacroscopic axonal connections in the human brain distribute information and neuronal activity across the brain. Although this complexity previously hindered elucidation of functional connectivity mechanisms, brain organoid technologies have recently provided novel avenues to investigate human brain function by constructing small segments of the brain in vitro. Here, we describe the neural activity of human cerebral organoids reciprocally connected by a bundle of axons. Compared to conventional organoids, connected organoids produced significantly more intense and complex oscillatory activity. Optogenetic manipulations revealed that the connected organoids could re-play and recapitulate over time temporal patterns found in external stimuli, indicating that the connected organoids were able to form and retain temporal memories. Our findings suggest that connected organoids may serve as powerful tools for investigating the roles of macroscopic circuits in the human brain – allowing researchers to dissect cellular functions in three-dimensional in vitro nervous system models in unprecedented ways.

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Slow ATP loss and the defense of ion homeostasis in the anoxic frog brain

Journal of Experimental Biology ◽

10.1242/jeb.204.20.3547 ◽

2001 ◽

Vol 204 (20) ◽

pp. 3547-3551

Author(s):

Debra L. Knickerbocker ◽

Peter L. Lutz

Keyword(s):

Initial Phase ◽

Ion Homeostasis ◽

Atp Depletion ◽

Neuronal Membrane ◽

Anoxia Tolerance ◽

Frog Brain ◽

Atp Levels ◽

Anoxic Depolarization ◽

Rate Of Increase ◽

The Brain

SUMMARY For most vertebrates, cutting off the oxygen supply to the brain results in a rapid (within minutes) loss of ATP, the failure of ATP-dependent ion-transport process, subsequent anoxic depolarization of neuronal membrane potential and consequential neuronal death. The few species that survive brain anoxia for days or months, such as the freshwater turtle Trachemys scripta, avoid anoxic depolarization and maintain brain ATP levels through a coordinated downregulation of brain energy demand processes. The frog Rana pipiens represents an intermediate in anoxia-tolerance, being able to survive brain anoxia for hours. However, the anoxic frog brain does not defend its energy stores. Instead, anoxia-tolerance appears to be related to a retarded rate of ATP depletion. To investigate the relationship between this slow ATP depletion and the loss of ionic homeostasis, cerebral extracellular K+ concentrations were monitored and ATP levels measured during anoxia, during the initial phase of anoxic depolarization and during complete anoxic depolarization. Extracellular K+ levels were maintained at normoxic levels for at least 3 h of anoxia, while ATP content decreased by 35 %. When ATP levels reached 0.33±0.06 mmol l–1 (mean ± s.e.m., N=5), extracellular K+ levels slowly started to increase. This value is thought to represent a critical ATP concentration for the maintenance of ion homeostasis. When extracellular [K+] reached an inflection value of 4.77±0.84 mmol l–1 (mean ± s.e.m., N=5), approximately 1 h later, the brain quickly depolarized. Part of the reduction in ATP demand was attributable to an approximately 50 % decrease in the rate of K+ efflux from the anoxic frog brain, which would also contribute to the retarded rate of increase in extracellular [K+] during the initial phase of anoxic depolarization. However, unlike the anoxia-tolerant turtle brain, adenosine did not appear to be involved in the downregulation of K+ leakage in the frog brain. The increased anoxia-tolerance of the frog brain is thought to be a matter more of slow death than of enhanced protective mechanisms.

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Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

Cells ◽

10.3390/cells9112476 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2476

Author(s):

Juliana González-Sanmiguel ◽

Christina M. A. P. Schuh ◽

Carola Muñoz-Montesino ◽

Pamina Contreras-Kallens ◽

Luis G. Aguayo ◽

...

Keyword(s):

Protein Misfolding ◽

Membrane Damage ◽

Amyloid Β ◽

Toxin Production ◽

Alpha Synuclein ◽

Oral Bacteria ◽

Special Focus ◽

Brain Invasion ◽

Potential Association ◽

The Brain

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Creutzfeldt–Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.

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Oxygen in tissues during deep hypothermia

Journal of Applied Physiology ◽

10.1152/jappl.1961.16.5.827 ◽

1961 ◽

Vol 16 (5) ◽

pp. 827-830 ◽

Cited By ~ 3

Author(s):

Y. K. Byon ◽

E. F. Adolph

Keyword(s):

Pulmonary Ventilation ◽

Oxygen Electrode ◽

Deep Hypothermia ◽

Systemic Blood ◽

Systemic Blood Flow ◽

Steady Current ◽

Leg Muscle ◽

Forced Breathing ◽

The One ◽

The Brain

An oxygen electrode and a thermistor were placed in the brain stem, leg muscle, or abdomen of a rat cooled to 17—15 C. When the rat was thereafter kept at 16∘the electrode usually showed a steady current. At 13—11∘ the apparent Po2 of tissue in most instances diminished during 2—3 hr unless artificial breathing was given. Forced breathing of air or oxygen ordinarily raised the Po2; of nitrogen usually, but not always, lowered the Po2. When the apparent Po2 was not thus raised or lowered, the flow of blood to the one tissue being examined, but not necessarily to all tissues, was evidently inadequate. The heart could be stopped reversibly by further cooling to 9—5∘; brain Po2 diminished only gradually at that low temperature. Survival was assured by a Po2 that was high and steady, but often occurred also after a diminishing or zero Po2. In the hypothermic rat, either pulmonary ventilation or systemic blood flow or an unidentified factor could limit the rat's survival. Submitted on October 26, 1960

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Environmental and Nutritional “Stressors” and Oligodendrocyte Dysfunction: Role of Mitochondrial and Endoplasmatic Reticulum Impairment

Biomedicines ◽

10.3390/biomedicines8120553 ◽

2020 ◽

Vol 8 (12) ◽

pp. 553

Author(s):

Jessica Maiuolo ◽

Micaela Gliozzi ◽

Vincenzo Musolino ◽

Cristina Carresi ◽

Saverio Nucera ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Energy Production ◽

Lipid Synthesis ◽

Main Function ◽

Cellular Functions ◽

Mitochondrial Oxidative Stress ◽

The Central Nervous System ◽

Altered Regulation ◽

The Brain

Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.

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Role of MicroRNAs in Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20225649 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5649 ◽

Cited By ~ 20

Author(s):

Suh Yee Goh ◽

Yin Xia Chao ◽

Shaikali Thameem Dheen ◽

Eng-King Tan ◽

Samuel Sam-Wah Tay

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Small Sample Size ◽

Small Sample ◽

Biological Molecules ◽

Incomplete Penetrance ◽

Cellular Functions ◽

Druggable Targets ◽

The Brain

Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.

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