Energetic metabolism in mouse cerebral cortex during chronic hypoxia

Cáceda, Ricardo; Gamboa, Jorge L.; Boero, Jaime; Monge-C, Carlos; Arregui, Alberto

doi:10.1016/s0304-3940(01)01630-5

Cited by 35 publications

(23 citation statements)

References 16 publications

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“…We expected the PCr/Cr ratio to be reduced because cytochrome c oxidase activity is decreased in chronic hypoxia [11,27] and because PCr acts as a temporary energy buffer when ATP production is inadequate [52]. Furthermore, the effect was present during both hypoxic conditions and hyperoxic testing states, suggesting that the increase was due to chronic hypoxia rather than to the sudden hyperoxic conditions during NMR studies.…”

Section: Discussionmentioning

confidence: 99%

“…Rodents that have been hypoxic during the early postnatal period demonstrate evidence of disrupted synaptic development [13], alterations in NMDA receptor expression and function [42], and alterations in key enzymes of glucose oxidative metabolism in the brain [26]. The activity of neuronal cytochrome c oxidase, a key enzyme in oxidative phosphorylation, is decreased in chronic hypoxia [11,27].…”

Section: Introductionmentioning

confidence: 99%

“…We hypothesized that chronic hypoxia would adversely affect the metabolite markers of energy metabolism, neuronal integrity, myelination, and neurotransmitters. We used a well-described rodent model of chronic postnatal hypoxia in our study [11,26,32]. Rats between the ages of postnatal day (P) 14 and P28 were studied because of the similarity between their hippocampal development and that of, respectively, a full-term human newborn infant and a 2-to 3-year-old child [4].…”

Section: Introductionmentioning

confidence: 99%

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In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Raman

Tkáč

Ennis

et al. 2005

Developmental Brain Research

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The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1 H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O 2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 Al centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios ( P b 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia. D 2005 Elsevier B.V. All rights reserved.Theme: Other systems of the CNS Topic: Brain metabolism and blood flow

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Raman

Tkáč

Ennis

et al. 2005

Developmental Brain Research

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“…It is more likely instead that the increase in glycolysis functions to balance the tissue acid-base disturbances, which are caused by hyperventilation induced decreased PaCO∑ (Lauro and LaManna, 1997). It is unknown whether brain oxygen consumption is depressed in hypoxicadapted rats; oxygen consumption has been reported to be unchanged in humans at altitude (Moller et al, 2002), but rat brain cytochrome oxidase is decreased by about 15% (Caceda et al, 2001;Chávez et al, 1995;LaManna et al, 1996), and Reprinted by permission from Sick et al (1982).…”

Section: Chronic Effects Of Hypoxiamentioning

confidence: 99%

Structural and functional adaptation to hypoxia in the rat brain

LaManna

Chávez

Pichiule

2004

Journal of Experimental Biology

176

162

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Chronic exposure to a hypoxic environment leads to structural and functional adaptations in the rat brain. One significant adaptation is a decrease in intercapillary distances through a near doubling of the capillary density, which begins after about 1 week of hypoxic exposure and is completed by 3 weeks. Hypoxic angiogenesis is controlled by activation of downstream genes by Hypoxia Inducible Factor-1 and Angiopoietin-2. The processes that increase capillary density are reversible upon restoration of the ambient oxygen concentration. Capillary regression, which also occurs over a 3-week period, is accomplished through activation of apoptosis. The implication from these observations is that the brain naturally functions in a low, but controlled, oxygen environment. Acute imbalances in oxygen delivery and metabolic demand are addressed through changes in blood flow; persistent imbalances activate mechanisms that adjust capillary density. The mechanisms that control these processes decline with age.

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“…31) Acute (short exposure) and chronic (long exposure) hypoxia induced decreases and increases in SUDH activities, respectively, of hepatic, renal and cerebral cells. 32,33) However, it was unclear whether the apoptosis was attributed to Sertoli cell damage caused directly by MBP or secondarily by a hypoxia due to MBP-induced hemoglobin deprivation. In the perfused testis, apoptosis was observed under the hypoxic condition (lower than 7% DO), but not on the 100 mM MBP perfusion using DNA laddering on gel electrophoresis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Possible Origin of Rat Testicular Atrophy Induced by Di-n-Butyl Phthalate: Changes in the Activities of Some Enzymes during Rat Testis Perfusion under a Hypoxic Condition and with Mono-n-Butyl Phthalate.

Watanabe

Shimizu

Matsumoto

et al. 2002

JOURNAL OF HEALTH SCIENCE

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To examine whether testicular toxicity in rats is caused by a direct effect of mono-butyl phthalate (MBP), a metabolite of di-butyl phthalate, or by a secondary effect attributed to a hypoxic condition due to the MBP-induced hemoglobin deprivation, the testes were perfused with a solution of MBP in Eagle's MEM or the MEM with/without oxygen, and the activities of testicular enzymes were measured. A decrease in the succinate dehydrogenase (SUDH) activity was observed by the hypoxic perfusate [20-30% dissolved oxygen (DO)], and an induction of apoptosis was observed by the 7% DO perfusate. However, the 100 mM MBP perfusate decreased the activity of SUDH per testis weight, but not per protein level. Therefore, this study proposes that the toxicity might be caused by hypoxia and a coincident depletion of SUDH activity, followed by an apoptotic testicular cell death.Key words ---di-n-butyl phthalate, mono-n-butyl phthalate, succinate dehydrogenase, testicular damage, testicular perfusion, hypoxia counts and in testicular enzyme activities, as well as by anti-androgenic effects and testicular atrophy in many reviews. Foster et al., 5) Fukuoka et al., [6][7][8][9] and Oishi and Hiraga 10) have addressed the strong evidences that the monoester is the active principle in inducing reproductive toxicity. We know relatively little about the toxic mechanism involved in time points by di-butyl phthalate (DBP) and/or its metabolite, mono-butyl phthalate (MBP), through which testicular damage is characterized by the sloughing of germ cells in histological findings, following decreases in the testicular levels of enzymes [including succinate dehydrogenase (SUDH)] at toxic doses at which the damage was monitored by testicular atrophy observed within one week after oral DBP-treatment. [5][6][7]11,12) A decrease in iron levels of both the blood and red blood cells (RBC) was observed to coincide with or prior to the decrease in SUDH activity of the Sertoli cells, accompanied by a decrease in the iron level of interstitial cells and an increase in the activity of lactate dehydrogenase (LDH) in the germ cells.

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Energetic metabolism in mouse cerebral cortex during chronic hypoxia

Cited by 35 publications

References 16 publications

In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Structural and functional adaptation to hypoxia in the rat brain

Possible Origin of Rat Testicular Atrophy Induced by Di-n-Butyl Phthalate: Changes in the Activities of Some Enzymes during Rat Testis Perfusion under a Hypoxic Condition and with Mono-n-Butyl Phthalate.

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