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Folic Acid potentiates the effect of memantine on spatial learning and neuronal protection in an Alzheimer's disease transgenic model.
J Alzheimers Dis. 2010; 20(2):607-15.JA

Abstract

Folic acid deficiency and hyperhomocysteinemia potentiate amyloid-beta (Abeta) 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 Abeta 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 Abeta40 and Abeta42 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 Abeta production, and modification of brain gene expression.

Authors+Show Affiliations

Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20164552

Citation

Chen, Ta-Fu, et al. "Folic Acid Potentiates the Effect of Memantine On Spatial Learning and Neuronal Protection in an Alzheimer's Disease Transgenic Model." Journal of Alzheimer's Disease : JAD, vol. 20, no. 2, 2010, pp. 607-15.
Chen TF, Huang RF, Lin SE, et al. Folic Acid potentiates the effect of memantine on spatial learning and neuronal protection in an Alzheimer's disease transgenic model. J Alzheimers Dis. 2010;20(2):607-15.
Chen, T. F., Huang, R. F., Lin, S. E., Lu, J. F., Tang, M. C., & Chiu, M. J. (2010). Folic Acid potentiates the effect of memantine on spatial learning and neuronal protection in an Alzheimer's disease transgenic model. Journal of Alzheimer's Disease : JAD, 20(2), 607-15. https://doi.org/10.3233/JAD-2010-1396
Chen TF, et al. Folic Acid Potentiates the Effect of Memantine On Spatial Learning and Neuronal Protection in an Alzheimer's Disease Transgenic Model. J Alzheimers Dis. 2010;20(2):607-15. PubMed PMID: 20164552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folic Acid potentiates the effect of memantine on spatial learning and neuronal protection in an Alzheimer's disease transgenic model. AU - Chen,Ta-Fu, AU - Huang,Rwei-Fen S, AU - Lin,Sey-En, AU - Lu,Jyh-Feng, AU - Tang,Ming-Chi, AU - Chiu,Ming-Jang, PY - 2010/2/19/entrez PY - 2010/2/19/pubmed PY - 2010/9/8/medline SP - 607 EP - 15 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 20 IS - 2 N2 - Folic acid deficiency and hyperhomocysteinemia potentiate amyloid-beta (Abeta) 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 Abeta 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 Abeta40 and Abeta42 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 Abeta production, and modification of brain gene expression. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20164552/Folic_Acid_potentiates_the_effect_of_memantine_on_spatial_learning_and_neuronal_protection_in_an_Alzheimer's_disease_transgenic_model_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-2010-1396 DB - PRIME DP - Unbound Medicine ER -