Effect of ageing on extracellular ascorbate concentration in rat brain

Svensson, Lennart; Wu, Chenggang; Hulthe, Peter; Johannessen, Kenn; Engel, Jo ̈rgen A.

doi:10.1016/0006-8993(93)90851-d

Cited by 29 publications

(13 citation statements)

References 32 publications

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“…The L-AA concentrations (0.2-1.0 mM) that increase neurosteroid accumulation are in the range of endogenous extracellular L-AA levels found by other investigators in rat brain under various experimental conditions (Chinoy, 1972;Stamford et al, 1984). L-AA, a vitamin for many species, including human, but not rat (Rose and Bode, 1993), displays several interesting properties: (a) it shows an uneven regional brain distribution (Stamford et al, 1984;Svensson et al, 1993); (b) it is taken up and stored by brain cells (Rose and Bode, 1993); (c) it can be released from neurons by a number of stimuli (Bigelow et al, 1984;Boutelle et al, 1989;Rebec, 1990, 1993); and (d) it modulates the binding characteristics and the function of neurotransmitter receptors (Snodgrass, 1992), including those for 5-HT (Muakkassah-Kelly et al, 1982). It is therefore conceivable that changes in the extracellular levels of L-AA, also as a consequence of synaptic activity, may in turn affect the function of neighboring neurotransmitter receptors.…”

Section: Discussionmentioning

confidence: 86%

Modulation of Neurosteroid Synthesis/Accumulation by l‐Ascorbic Acid in Rat Brain Tissue: Inhibition by Selected Serotonin Antagonists

Roscetti

Carmine

Trabucchi

et al. 1998

Journal of Neurochemistry

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We have investigated the possibility that the synthesis/accumulation of neurosteroids, i.e., brain‐produced steroids putatively endowed with modulatory actions in the CNS, is regulated by monoaminergic receptor‐mediated mechanisms. In minces of rat brain cortex, l‐ascorbic acid concentration‐dependently (0.07–1.0 mM) increases the levels of pregnenolone, allotetrahydrodeoxycorticosterone, and dehydroepiandrosterone. This effect of l‐ascorbic acid is region‐dependent: in hippocampus, progesterone and allopregnanolone are also increased, whereas dehydroepiandrosterone is unchanged, and in corpus striatum only progesterone is increased significantly. 5‐Hydroxytryptamine (10 µM), 1‐(3‐chlorophenyl)piperazine (1.0 µM), and 5‐methoxytryptamine (0.4 µM) mimic the effect of l‐ascorbic acid, whereas a pretreatment with p‐chlorophenylalanine (400 mg/kg i.p., 2 days) reduces the amplitude of the l‐ascorbic acid effect on brain cortical neurosteroids. The effect of l‐ascorbic acid is blocked by the nonselective serotonin antagonists methiothepin, clozapine, methysergide, and pizotifen, but not mesulergine, spiperone, MDL 72222, and dl‐propranolol, nor by the catecholaminergic receptor antagonists prazosin and S(−)‐sulpiride. l‐Ascorbic acid is not additive with dibutyryl‐cyclic AMP and, furthermore, the inhibition of adenylate cyclase by MDL 12330A, but not of phospholipase C by U‐73122, markedly attenuates the l‐ascorbic acid‐induced increase of pregnenolone in rat brain cortical minces. Together these data suggest that l‐ascorbic acid plays a role in the modulation of neurosteroidogenesis, presumably by favoring the activation of the purported serotonin type 6 receptor by endogenous serotonin.

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Section: Discussionmentioning

confidence: 86%

Modulation of Neurosteroid Synthesis/Accumulation by l‐Ascorbic Acid in Rat Brain Tissue: Inhibition by Selected Serotonin Antagonists

Roscetti

Carmine

Trabucchi

et al. 1998

Journal of Neurochemistry

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“…Published data suggest that the Asc concentration declines with age (42,43). However, it is unclear whether this phenomenon occurs during the process of development or aging, as most previous studies have focused on development.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

et al. 2011

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In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited 1H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.

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“…The lower CSD velocity found in aged animals is apparently contrasting with the tendency of the aged brain in presenting higher levels of lipid peroxidation, which lead to the formation of ROS 36 and would accelerate CSD. However, in the rat brain the levels of the antioxidant molecule ascorbic acid (AA) are preserved in the aged cerebral cortex, 37 and this could help explaining the lower CSD velocity in the aged rat. Other brain changes related to aging such as alteration of the intraand extracellular brain volumes 38 may also help in explaining this effect.…”

Section: Csd Aging and Dietary Antioxidantsmentioning

confidence: 99%

The use of cortical spreading depression for studying the brain actions of antioxidants

Guedes

Abadie-Guedes

Bezerra

2012

Nutritional Neuroscience

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Effect of ageing on extracellular ascorbate concentration in rat brain

Cited by 29 publications

References 32 publications

Modulation of Neurosteroid Synthesis/Accumulation by l‐Ascorbic Acid in Rat Brain Tissue: Inhibition by Selected Serotonin Antagonists

Modulation of Neurosteroid Synthesis/Accumulation by l‐Ascorbic Acid in Rat Brain Tissue: Inhibition by Selected Serotonin Antagonists

Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

The use of cortical spreading depression for studying the brain actions of antioxidants

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