Membrane lipids and morphology of brain cortex synaptosomes isolated from hibernating Yakutian ground squirrel

Kolomiytseva, I. K.; Perepelkina, N. I.; Zharikova, Alevtina D.; Popov, V.I.

doi:10.1016/j.cbpb.2008.08.001

Cited by 25 publications

(8 citation statements)

References 29 publications

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“…Impairment of myelin formation has been observed in the brains of mouse models of long-term type 1 diabetes (Francis et al, 2008). Reduced cholesterol content in cortical synaptosomes and microsomes is also observed in the Yakutian ground squirrel during hibernation (Kolomiytseva et al, 2008). Our findings suggest that the hypoinsulinemia induced by prolonged starvation during hibernation could lead to down-regulation of SREBP-2 in brain resulting in these changes.…”

Section: Discussionmentioning

confidence: 95%

“…Synaptosomes were isolated using discontinuous sucrose density gradient centrifugation (Kolomiytseva et al, 2008) as detailed in Supplemental Experimental Procedures.…”

Section: Methodsmentioning

confidence: 99%

“…(B) Cholesterol content in the synaptosomal membrane extracted from the frontal cortex of control (n = 4) and STZ-diabetic (n = 4) mice 18 days after STZ administration. Synaptosome-rich fraction was separated from myelin fraction by discontinuous sucrose gradient centrifugation as shown on the left (Kolomiytseva et al, 2008). The synaptosomal cholesterol content in μg per mg protein is shown on the right.…”

Section: Figurementioning

confidence: 99%

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Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

et al. 2010

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Summary The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis, and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells, and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation, and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.

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Section: Discussionmentioning

confidence: 95%

“…Synaptosomes were isolated using discontinuous sucrose density gradient centrifugation (Kolomiytseva et al, 2008) as detailed in Supplemental Experimental Procedures.…”

Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

et al. 2010

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“…In addition, cytoskeletal changes leading to significantly elevated resistance to acid hemolysis have been described in red cells from hibernating as compared to summer-active ground squirrels [24]. Furthermore, membrane lipid composition is altered in both RBCs [25] and brain synaptosomes [26] isolated from hibernating ground squirrels, but the functional significance of such changes remains unknown. One might presume that altering lipid composition could serve to maintain homeoviscous adaptation but supporting data are not yet available.…”

Section: Introductionmentioning

confidence: 95%

Vertebrate cell death in energy-limited conditions and how to avoid it: what we might learn from mammalian hibernators and other stress-tolerant vertebrates

2010

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Dormancy in vertebrates may expose cells to acidosis, hypoxia/anoxia, oxidative damage, and extremes in temperature. All of these insults are known to be pro-apoptotic in typical vertebrate cells, especially mammals. Since dormancy is presumably the result of a need for energy conservation, the inherent energetic demand of replenishing cells that underwent apoptosis seems at odds with this strategy. This review will discuss processes to mitigate apoptosis and how these processes might be regulated in stress-tolerant vertebrates such as mammalian hibernators. As data directly addressing such issues are scarce and often conflicting, an apparently complex regulation of apoptosis seems to be at work. For example, apoptosis is mitigated during dormancy, key signaling events including the activation of caspase-3 may still occur. However, both passive, temperature-induced depression of apoptotic signaling as well as active suppression of apoptosis appear to work in synergy in these systems. In many instances cell death is prevented by simply avoiding the cellular triggers (e.g. leakage of proteins from the mitochondria or increases in intracellular calcium) that initiate apoptotic signaling. In this review we discuss what is known about programmed cell death in these under-studied models and highlight features of their physiology that likely support survival in the face of conditions that would induce cell death in typical vertebrate cells.

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“…The lipid composition of the cell membrane changes with alterations in the environment, and this change depends on the synthesis, metabolism and intermembrane transfer of the lipid. It was shown that lipids of membranes and cellular organelles of mammalian brain are involved in the adaptation to low temperatures [69]. In normal rat brains, the nuclear fractions of neurons and neuroglia are depleted of phospholipids and cholesterol and enriched in mono- and diglycerides and fatty acids.…”

Section: Pharmacological Targets For Drug Developmentmentioning

confidence: 99%

Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect

Han¹,

Park²,

Kim³

et al. 2012

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Induced therapeutic hypothermia is the one of the most effective tools against brain injury and inflammation. Even though its beneficial effects are well known, there are a lot of pitfalls to overcome, since the potential adverse effects of systemic hypothermia are still troublesome. Without the knowledge of the precise mechanisms of hypothermia, it will be difficult to tackle the application of hypothermia in clinical fields. Better understanding of the characteristics and modes of hypothermic actions may further extend the usage of hypothermia by developing novel drugs based on the hypothermic mechanisms or by combining hypothermia with other therapeutic modalities such as neuroprotective drugs. In this review, we describe the potential therapeutic targets for the development of new drugs, with a focus on signal pathways, gene expression, and structural changes of cells. Theapeutic hypothermia has been shown to attenuate neuroinflammation by reducing the production of reactive oxygen species and proinflammatory mediators in the central nervous system. Along with the mechanism-based drug targets, applications of therapeutic hypothermia in combination with drug treatment will also be discussed in this review.

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Membrane lipids and morphology of brain cortex synaptosomes isolated from hibernating Yakutian ground squirrel

Cited by 25 publications

References 29 publications

Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

Vertebrate cell death in energy-limited conditions and how to avoid it: what we might learn from mammalian hibernators and other stress-tolerant vertebrates

Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect

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