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Preferential Accumulation of 14C-N-Glycolylneuraminic Acid over 14C-N-Acetylneuraminic Acid in the Rat Brain after Tail Vein Injection.

Taguchi R, Minami A, Matsuda Y, Takahashi T, Otsubo T, Ikeda K, Suzuki T - PLoS ONE (2015)

Bottom Line: Brain autoradiography indicated that 14C-Neu5Gc was accumulated predominantly in the hippocampus. 14C-Neu5Gc transferred into the brain was incorporated into gangliosides including GM1, GD1a, GD1b, GT1b and GQ1b.Reduction of 14C-Neu5Gc after intracerebroventricular infusion was slower than that of 14C-Neu5Ac in the brain and hippocampus.The results suggest that Neu5Gc is transferred from blood into the brain across the blood brain barrier and accumulates in the brain more preferentially than does Neu5Ac.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

ABSTRACT
The two main molecular species of sialic acid existing in nature are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Neu5Ac is abundant in mammalian brains and plays crucial roles in many neural functions. In contrast, Neu5Gc is present only at a trace level in vertebrate brains. The brain-specific suppression of Neu5Gc synthesis, which is a common feature in mammals, suggests that Neu5Gc has toxicity against brain functions. However, in vivo kinetics of Neu5Gc in the whole body, especially in the brain, has not been studied in sufficient detail. To determine the in vivo kinetics of Neu5Gc, 14C-Neu5Gc was enzymatically synthesized and injected into rat tail veins. Although most of 14C-Neu5Gc was excreted in urine, a small amount of 14C-Neu5Gc was detected in the brain. Brain autoradiography indicated that 14C-Neu5Gc was accumulated predominantly in the hippocampus. 14C-Neu5Gc transferred into the brain was incorporated into gangliosides including GM1, GD1a, GD1b, GT1b and GQ1b. Reduction of 14C-Neu5Gc after intracerebroventricular infusion was slower than that of 14C-Neu5Ac in the brain and hippocampus. The results suggest that Neu5Gc is transferred from blood into the brain across the blood brain barrier and accumulates in the brain more preferentially than does Neu5Ac.

No MeSH data available.


Related in: MedlinePlus

Autoradiograms of 14C-Neu5Gc and 14C-Neu5Ac in the brain after tail vein injection.Autoradiography of the rat brain was performed at 3 hours after tail vein injection of 14C-Neu5Gc (A) or 14C-Neu5Ac (B). The experiment was performed twice, and the autoradiograms obtained were almost identical. O, olfactory bulb; S, striatum; H, hippocampus; T, thalamus; P, periaqueductal gray; C, cerebellum; M, medulla. Scale bar, 5 mm.
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pone.0131061.g004: Autoradiograms of 14C-Neu5Gc and 14C-Neu5Ac in the brain after tail vein injection.Autoradiography of the rat brain was performed at 3 hours after tail vein injection of 14C-Neu5Gc (A) or 14C-Neu5Ac (B). The experiment was performed twice, and the autoradiograms obtained were almost identical. O, olfactory bulb; S, striatum; H, hippocampus; T, thalamus; P, periaqueductal gray; C, cerebellum; M, medulla. Scale bar, 5 mm.

Mentions: By using autoradiography, we next determined the detailed distribution of radioactivity in the brain at 3 hr after tail vein injection of 14C-Neu5Gc. Although radioactivity was detected from all observed brain regions including the olfactory bulb, striatum, thalamus, periaqueductal gray, cerebellum and medulla, the hippocampus showed intense radioactivity (Fig 4). A similar tendency was obtained by radioactivity quantification. The hippocampus (8.94 ± 3.28 Bq/g tissue) showed higher radioactivity than that of the cerebellum (4.73 ± 0.50 Bq/g tissue) after 14C-Neu5Gc injection. In the case of 14C-Neu5Ac, radioactivity was also detected from all observed brain regions, but its signal intensity was weak compared to that of 14C-Neu5Gc (Fig 4). Radioactivity in the hippocampus (2.76 ± 0.31 Bq/g tissue) after 14C-Neu5Ac injection was also higher than that in the cerebellum (2.31 ± 0.31 Bq/g tissue).


Preferential Accumulation of 14C-N-Glycolylneuraminic Acid over 14C-N-Acetylneuraminic Acid in the Rat Brain after Tail Vein Injection.

Taguchi R, Minami A, Matsuda Y, Takahashi T, Otsubo T, Ikeda K, Suzuki T - PLoS ONE (2015)

Autoradiograms of 14C-Neu5Gc and 14C-Neu5Ac in the brain after tail vein injection.Autoradiography of the rat brain was performed at 3 hours after tail vein injection of 14C-Neu5Gc (A) or 14C-Neu5Ac (B). The experiment was performed twice, and the autoradiograms obtained were almost identical. O, olfactory bulb; S, striatum; H, hippocampus; T, thalamus; P, periaqueductal gray; C, cerebellum; M, medulla. Scale bar, 5 mm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476740&req=5

pone.0131061.g004: Autoradiograms of 14C-Neu5Gc and 14C-Neu5Ac in the brain after tail vein injection.Autoradiography of the rat brain was performed at 3 hours after tail vein injection of 14C-Neu5Gc (A) or 14C-Neu5Ac (B). The experiment was performed twice, and the autoradiograms obtained were almost identical. O, olfactory bulb; S, striatum; H, hippocampus; T, thalamus; P, periaqueductal gray; C, cerebellum; M, medulla. Scale bar, 5 mm.
Mentions: By using autoradiography, we next determined the detailed distribution of radioactivity in the brain at 3 hr after tail vein injection of 14C-Neu5Gc. Although radioactivity was detected from all observed brain regions including the olfactory bulb, striatum, thalamus, periaqueductal gray, cerebellum and medulla, the hippocampus showed intense radioactivity (Fig 4). A similar tendency was obtained by radioactivity quantification. The hippocampus (8.94 ± 3.28 Bq/g tissue) showed higher radioactivity than that of the cerebellum (4.73 ± 0.50 Bq/g tissue) after 14C-Neu5Gc injection. In the case of 14C-Neu5Ac, radioactivity was also detected from all observed brain regions, but its signal intensity was weak compared to that of 14C-Neu5Gc (Fig 4). Radioactivity in the hippocampus (2.76 ± 0.31 Bq/g tissue) after 14C-Neu5Ac injection was also higher than that in the cerebellum (2.31 ± 0.31 Bq/g tissue).

Bottom Line: Brain autoradiography indicated that 14C-Neu5Gc was accumulated predominantly in the hippocampus. 14C-Neu5Gc transferred into the brain was incorporated into gangliosides including GM1, GD1a, GD1b, GT1b and GQ1b.Reduction of 14C-Neu5Gc after intracerebroventricular infusion was slower than that of 14C-Neu5Ac in the brain and hippocampus.The results suggest that Neu5Gc is transferred from blood into the brain across the blood brain barrier and accumulates in the brain more preferentially than does Neu5Ac.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

ABSTRACT
The two main molecular species of sialic acid existing in nature are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Neu5Ac is abundant in mammalian brains and plays crucial roles in many neural functions. In contrast, Neu5Gc is present only at a trace level in vertebrate brains. The brain-specific suppression of Neu5Gc synthesis, which is a common feature in mammals, suggests that Neu5Gc has toxicity against brain functions. However, in vivo kinetics of Neu5Gc in the whole body, especially in the brain, has not been studied in sufficient detail. To determine the in vivo kinetics of Neu5Gc, 14C-Neu5Gc was enzymatically synthesized and injected into rat tail veins. Although most of 14C-Neu5Gc was excreted in urine, a small amount of 14C-Neu5Gc was detected in the brain. Brain autoradiography indicated that 14C-Neu5Gc was accumulated predominantly in the hippocampus. 14C-Neu5Gc transferred into the brain was incorporated into gangliosides including GM1, GD1a, GD1b, GT1b and GQ1b. Reduction of 14C-Neu5Gc after intracerebroventricular infusion was slower than that of 14C-Neu5Ac in the brain and hippocampus. The results suggest that Neu5Gc is transferred from blood into the brain across the blood brain barrier and accumulates in the brain more preferentially than does Neu5Ac.

No MeSH data available.


Related in: MedlinePlus