Asfotase alfa restores PLP-dependent GABA, cystathionine, and amino acid metabolism in a mouse model of hypophosphatasia

IF 2.4 4区医学 Q3 NEUROSCIENCES

Neuroscience Research Pub Date : 2025-07-11 DOI:10.1016/j.neures.2025.104940

Kathryn N. Phoenix , Andre Marozsan , Susan Liu-Chen , Lizhong Zhang , Amit Mogha , Yan Wong , Catherine A. Brownstein , Raja Padidela

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引用次数: 0

Abstract

This study assessed whether asfotase alfa treatment in Akp2^-/- mice (a model of hypophosphatasia) reversibly normalizes GABA and cystathionine in brain tissue to concentrations in wild-type mice. To do this, metabolite concentrations were analyzed at postnatal days 10 and 48. The data showed that asfotase alfa treatment significantly increased GABA concentrations and significantly decreased cystathionine concentrations in Akp2^-/- mice compared with vehicle-treated Akp2^-/- mice (GABA: 1.28 ± 0.03 vs 0.48 ± 0.02 μmol/g [P < 0.0001]; cystathionine: 0.06 ± 0.00 vs 0.60 ± 0.02 μmol/g [P < 0.0001]). Concentrations post-treatment were similar to those in wild-type mice. Asfotase alfa withdrawal negated these effects. These analyses demonstrated that asfotase alfa restores GABA and cystathionine concentrations in a murine model of hypophosphatasia.

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在低磷酸症小鼠模型中，Asfotase α恢复plp依赖的GABA、胱胱甘氨酸和氨基酸代谢。

本研究评估了在Akp2-/-小鼠（低磷酸症模型）中使用asfotase α fa是否可逆地使脑组织中GABA和半胱硫氨酸的浓度恢复到野生型小鼠的水平。为此，在出生后第10天和第48天分析代谢物浓度。结果表明，与Akp2-/-小鼠相比，asfotase α fa处理显著提高了Akp2-/-小鼠GABA浓度，显著降低了Akp2-/-小鼠胱硫氨酸浓度（GABA: 1.28±0.03 μmol/g vs 0.48±0.02 μmol/g）

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience Research 医学-神经科学

CiteScore

5.60

自引率

3.40%

发文量

136

审稿时长

28 days

期刊介绍： The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.