A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice

被引：93

作者：

Acuna, Anibal I. ^{[1
,2
,3
]}

Esparza, Magdalena ^{[1
,2
]}

Kramm, Carlos ^{[1
,2
]}

Beltran, Felipe A. ^{[1
,2
,3
]}

Parra, Alejandra V. ^{[1
,2
]}

Cepeda, Carlos ^{[4
]}

Toro, Carlos A. ^{[3
,5
]}

Vidal, Rene L. ^{[6
]}

Hetz, Claudio ^{[7
]}

Concha, Ilona I. ^{[1
]}

Brauchi, Sebastian ^{[2
,5
]}

Levine, Michael S. ^{[4
]}

Castro, Maite A. ^{[1
,2
]}

机构：

[1] Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Valdivia 5090000, Chile

[2] Univ Austral Chile, Ctr Invest Sur Austral Enfermedades Sistema Nervi, Valdivia 5090000, Chile

[3] Univ Austral Chile, Fac Ciencias, Escuela Grad, Valdivia 5090000, Chile

[4] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Inst Neurosci & Human Behav,Intellectual & Dev Di, Los Angeles, CA 90095 USA

[5] Univ Austral Chile, Fac Med, Inst Fisiol, Valdivia 5090000, Chile

[6] Univ Chile, Inst Ciencias Biomed, Santiago, Chile

[7] Neuroun Biomed Fdn, Santiago, Chile

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

INTRACELLULAR ASCORBIC-ACID; MOUSE MODEL; GLUCOSE CONSUMPTION; STRIATAL ASCORBATE; TRANSPORT; CELLS; NEURONS; INTERNALIZATION; STIMULATION; ENDOCYTOSIS;

D O I：

10.1038/ncomms3917

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Huntington's disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neurons could lead to early metabolic failure promoting neuronal death.

引用

页数：13

共 52 条

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