Research Papers: Gerotarget (Focus on Aging):

Gavage of D-Ribose induces Aβ-like deposits, Tau hyperphosphorylation as well as memory loss and anxiety-like behavior in mice

Beibei Wu, Yan Wei, Yujing Wang, Tao Su, Lei Zhou, Ying Liu and Rongqiao He _

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Oncotarget. 2015; 6:34128-34142. https://doi.org/10.18632/oncotarget.6021

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Beibei Wu1,4,*, Yan Wei1,*, Yujing Wang1,4, Tao Su1, Lei Zhou5, Ying Liu1 and Rongqiao He1,2,3

1 State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China

3 Alzheimer’s Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China

4 University of Chinese Academy of Sciences, Beijing, China

5 Animal Experiment Center, Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

* These authors have contributed equally to this work

Correspondence to:

Rongqiao He, email:

Keywords: D-Ribose, memory impairment, Tau hyperphosphorylation, Aβ-like deposition, anxiety-like behavior, Gerotarget

Received: August 29, 2015 Accepted: September 07, 2015 Published: October 07, 2015


In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. Aβ-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates Aβ-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for age-related cognitive impairment and diabetic encephalopathy.

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