Estrogen-dependent modulation of rat brain ascorbate levels and ischemia-induced ascorbate loss

Kume-Kick, June; Rice, Margaret E.

doi:10.1016/s0006-8993(98)00628-3

Cited by 51 publications

(27 citation statements)

References 49 publications

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“…3,8,34 However, it is interesting to note that the intact females in the present study were neuroprotected compared with OVX rats, despite having circulating E 2 levels, during most of their estrous cycles, similar to the levels seen in the OVX group. Whether the relatively brief E 2 surge occurring on the day of proestrus or some other factor, such as progesterone, can account for the relative neuroprotection seen in the intact females remains to be established.…”

supporting

confidence: 56%

“…7,8 These findings would appear to be consistent with a nongenomic process and might be viewed as evidence of antioxidant actions of estrogens, as some investigators have suggested. 26,27,33,34 On the other hand, there are indications that E 2 -related neuroprotection, to some degree, may involve interactions with classic receptors (see, for example, Singer et al 35 ). The present finding of detectable blood E 2 levels in the OVX rats (30 pg ⅐ mL…”

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confidence: 99%

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Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats

Wang

Santizo

Baughman

et al. 1999

Stroke

156

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Background and Purpose-Estrogen-related neuroprotection in association with animal models of transient forebrain and focal ischemia has been documented in several recent reports. Some of those studies indicated that part of that benefit was a function of improved intraischemic vasodilating capacity. In the present study we examined whether chronic estrogen depletion and repletion affected ischemic neuropathology through perfusion-independent mechanisms. Methods-Normal, ovariectomized (OVX), and OVX female rats treated with 17␤-estradiol (E 2 ) were subjected to 30 minutes of transient forebrain ischemia (right common carotid occlusion plus hemorrhagic hypotension) and reperfusion. Neurological function and brain histopathology were assessed over the 72-hour recovery period. In all rats, preischemic and intraischemic cortical cerebral blood flow (CBF) levels were monitored with laser-Doppler flowmetry.In additional rats, CBF changes in the striatum and hippocampus were also monitored with laser-Doppler flowmetry probes and radiolabeled microspheres. In each experiment, the level of ischemia was targeted to a 75% to 80% reduction in cortical CBF. Results-The similarity in ischemic severity among groups was supported by measurements of comparable patterns of electroencephalographic power changes during the ischemic period. Compared with normal females, OVX rats showed diminished neurological outcomes and more severe histopathology in the hippocampus and striatum. Two-week treatment of OVX rats with E 2 was accompanied by postischemic neuropathological changes similar to those seen in normal females. Intraischemic CBF reductions in the hippocampus and striatum were similar in all groups (to 35% to 50% of the preischemic value) but significantly less than the cortical CBF reductions. Conclusions-These findings indicate that estrogen provides ischemic neuroprotection through mechanisms unrelated to improvement of intraischemic cerebral perfusion. (Stroke. 1999;30:630-637.)

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supporting

confidence: 56%

mentioning

confidence: 99%

Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats

Wang

Santizo

Baughman

et al. 1999

Stroke

156

View full text Add to dashboard Cite

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“…Although we did not see differences in basal AA concentrations in striatum, we did observe a trend toward lower levels in female mice compared to males and we observed lower levels in female KI compared to female WT mice (Table 1). Since sex differences in brain AA function are region specific [13], it is difficult to determine how past findings relate to what we have observed in the striatum. It is probable, however, that gonadal hormones such as estrogen contribute to the differences we have observed and play a role in modulating striatal AA release.…”

Section: Discussionmentioning

confidence: 82%

“…It is probable, however, that gonadal hormones such as estrogen contribute to the differences we have observed and play a role in modulating striatal AA release. Estrogen modulates brain AA levels and prevented ischemia-induced AA loss in the hippocampus [13]. Like ischemia, HD also results in oxidative stress which may account for the striatal AA loss observed in male mice.…”

Section: Discussionmentioning

confidence: 93%

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Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington's disease

Dorner

Miller

Barton

et al. 2007

Behavioural Brain Research

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Ethological assessment of murine models of Huntington's disease (HD), an inherited neurodegenerative disorder, enables correlation between phenotype and pathophysiology. Currently, the most characterized model is the R6/2 line that develops a progressive behavioral and neurological phenotype by six weeks of age. A recently developed knock-in model with 140 CAG repeats (KI) exhibits a subtle phenotype with a longer progressive course, more typical of adult-onset HD in humans. We evaluated rotarod performance, open-field behavior, and motor activity across the diurnal cycle in KI mice during early to mid-adulthood. Although we did not observe any effects of age, relative to wild-type (WT) mice, KI mice showed significant deficits in both open-field climbing behavior and home-cage running wheel activity during the light phase of the diurnal cycle. An interesting sex difference also emerged. KI females spent more time in the open-field grooming and more time running during the diurnal dark phase than KI males and WT mice of both sexes. In striatum, the primary site of HD pathology, we measured behavior-related changes in extracellular ascorbate (AA), which is abnormally low in the R6/2 line, consistent with a loss of antioxidant protection in HD. KI males exhibited a 20-40% decrease in striatal AA from anesthesia baseline to behavioral activation that was not observed in other groups. Collectively, our results indicate behavioral deficits in KI mice that may be specific to the diurnal cycle. Furthermore, sex differences observed in behavior and striatal AA release suggest sex-dependent variation in the phenotype and neuropathology of HD.

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Repair of Protein Radicals by Antioxidants

Domazou¹,

Gebicki²,

Nauser³

et al. 2014

Israel Journal of Chemistry

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In vivo, proteins are the main targets for radicals and other reactive species. Their reactions result in formation of amino acid radicals on the protein surface that often yield tryptophan and tyrosyl radicals or, in the presence of O2, protein peroxyl radicals and hydroperoxides. All these species may propagate damage to biomolecules. Low molecular weight antioxidants, such as ascorbate, urate, and glutathione, are part of the defense system and function by repairing damaged proteins. We briefly review the existing knowledge about protein and amino acid radicals and their repair by antioxidants, including results of our investigations. The main question addressed is whether the antioxidants ascorbate, urate, and glutathione are able to repair amino acid radicals in model compounds and in proteins in vitro by pulse radiolysis. We show that ascorbate and urate repair tryptophan and tyrosyl radicals efficiently and inhibit proton‐coupled electron transfer from tyrosine residues to tryptophan radicals in a number of proteins. In contrast, repair by glutathione is much slower. Ascorbate also rapidly reduces the peroxyl radicals of the N‐acetylamide derivatives of glycine, alanine, and proline, whereas glutathione reduces peroxyl radicals in lysozyme. In vivo urate, ascorbate, and glutathione may prevent biological damage or, at least, reduce its rate, because they: (a) repair tryptophan and tyrosyl radicals in proteins and (b) reduce protein peroxyl radicals to the corresponding protein hydroperoxides. Most likely, in vivo, ascorbate and glutathione do not inhibit the reaction of C‐centered amino acid radicals with O2. Glutathione is less efficient that urate and ascorbate in repairing protein radicals; furthermore, the resulting glutathiyl radical is harmful. Ascorbate may be the more important repair agent in cells and tissues characterized by high ascorbate concentrations, such as the lens and brain; urate may be mainly responsible for repair in tissue compartments with higher urate concentrations, such as in plasma and saliva.

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Estrogen-dependent modulation of rat brain ascorbate levels and ischemia-induced ascorbate loss

Cited by 51 publications

References 49 publications

Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats

Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats

Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington's disease

Repair of Protein Radicals by Antioxidants

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