Folic acid potentiates the effect of memantine on spatial learning and neuronal protection in an alzheimer's disease transgenic model

Ta Fu Chen, Rwei Fen S. Huang, Sey En Lin, Jyh Feng Lu, Ming Chi Tang, Ming Jang Chiu

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)

摘要

Folic acid deficiency and hyperhomocysteinemia potentiate amyloid-β (Aβ) neuron toxicity. Memantine, an NMDA antagonist used in moderate to severe AD, is considered to be neuroprotective. We propose that folic acid might have a synergistic effect for memantine in protecting neurons from Aβ accumulation. We treated 8-month-old Tg2576 transgenic mice with memantine (30 mg/kg/day) with or without folic acid (8 mg/kg/day) for 4 months. Escape latencies in the Morris water maze were significantly shorter in the folic acid-memantine treatment group Tg(+)-M+F compared to both the non-treatment transgenic controls Tg(+) and the memantine-treatment group Tg(+)-M (both p < 0.05). Analysis of Aβ{40} and Aβ{42} showed lower brain loads in both treatment groups but this did not reach statistical significance. Histopathology analysis showed that Tg(+)-M+F had lower ratios of neuronal damage than Tg(+) (p < 0.001) and Tg(+)-M (p< 0.005). DNA analysis revealed that in the Tg(+)M-+F group, transcription was upregulated in 72 brain genes involved in neurogenesis, neural differentiation, memory, and neurotransmission compared to the Tg(+)-M group. In conclusion, we found that folic acid may potentiate the effect of memantine on spatial learning and neuronal protection. The benefit of combination therapy may be through co-action on the methylation-controlled Aβ production, and modification of brain gene expression.

原文英語
頁(從 - 到)607-615
頁數9
期刊Journal of Alzheimer's Disease
20
發行號2
DOIs
出版狀態已發佈 - 2010

ASJC Scopus subject areas

  • 老年病學和老年學
  • 精神病學和心理健康
  • 臨床心理學
  • 一般神經科學

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