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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

Preferential accumulation of 14C-Neu5Gc over 14C-Neu5Ac in the brain.Radioactivities in the brain (A), hippocampus (B), cerebellum (C) and blood (D) at 1, 3 and 24 hr after tail vein injection of 14C-Neu5Gc (n = 5) or 14C-Neu5Ac (n = 5–6) are shown as relative values to the radioactivities of injected-14C-Neu5Gc or 14C-Neu5Ac. *P < 0.05 and ***P < 0.001. of 14C-Neu5Gc or 14C-Neu5Ac.
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pone.0131061.g003: Preferential accumulation of 14C-Neu5Gc over 14C-Neu5Ac in the brain.Radioactivities in the brain (A), hippocampus (B), cerebellum (C) and blood (D) at 1, 3 and 24 hr after tail vein injection of 14C-Neu5Gc (n = 5) or 14C-Neu5Ac (n = 5–6) are shown as relative values to the radioactivities of injected-14C-Neu5Gc or 14C-Neu5Ac. *P < 0.05 and ***P < 0.001. of 14C-Neu5Gc or 14C-Neu5Ac.

Mentions: To investigate the difference between in vivo kinetics of Neu5Gc and that of Neu5Ac in the brain, radioactivity of 14C-Neu5Gc and that of 14C-Neu5Ac were compared after tail vein injection. After 14C-Neu5Gc injection, radioactivity in the brain reached a maximum level at 3 hr. In contrast, radioactivity after 14C-Neu5Ac injection reached a plateau in less than 1 hr and did not significantly change over a period of 24 hr (Fig 3A). 14C-Neu5Gc showed preferential accumulation over 14C-Neu5Ac in the brain and hippocampus (Fig 3A and 3B). In the cerebellum and blood, the amounts of 14C-Neu5Gc and 14C-Neu5Ac were not significantly different (Fig 3C and 3D).


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)

Preferential accumulation of 14C-Neu5Gc over 14C-Neu5Ac in the brain.Radioactivities in the brain (A), hippocampus (B), cerebellum (C) and blood (D) at 1, 3 and 24 hr after tail vein injection of 14C-Neu5Gc (n = 5) or 14C-Neu5Ac (n = 5–6) are shown as relative values to the radioactivities of injected-14C-Neu5Gc or 14C-Neu5Ac. *P < 0.05 and ***P < 0.001. of 14C-Neu5Gc or 14C-Neu5Ac.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476740&req=5

pone.0131061.g003: Preferential accumulation of 14C-Neu5Gc over 14C-Neu5Ac in the brain.Radioactivities in the brain (A), hippocampus (B), cerebellum (C) and blood (D) at 1, 3 and 24 hr after tail vein injection of 14C-Neu5Gc (n = 5) or 14C-Neu5Ac (n = 5–6) are shown as relative values to the radioactivities of injected-14C-Neu5Gc or 14C-Neu5Ac. *P < 0.05 and ***P < 0.001. of 14C-Neu5Gc or 14C-Neu5Ac.
Mentions: To investigate the difference between in vivo kinetics of Neu5Gc and that of Neu5Ac in the brain, radioactivity of 14C-Neu5Gc and that of 14C-Neu5Ac were compared after tail vein injection. After 14C-Neu5Gc injection, radioactivity in the brain reached a maximum level at 3 hr. In contrast, radioactivity after 14C-Neu5Ac injection reached a plateau in less than 1 hr and did not significantly change over a period of 24 hr (Fig 3A). 14C-Neu5Gc showed preferential accumulation over 14C-Neu5Ac in the brain and hippocampus (Fig 3A and 3B). In the cerebellum and blood, the amounts of 14C-Neu5Gc and 14C-Neu5Ac were not significantly different (Fig 3C and 3D).

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