Ying Huang1, Xian Huang2, Ling Zhang2, Fang Han1, Ke-Liang Pang1, Xue Li2, Jian-Ying Shen2,3. 1. School of Pharmaceutical Sciences, Tsinghua University, Beijing, China. 2. School of Medicine, Tsinghua University, Beijing, China. 3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Abstract
BACKGROUND: Environmental enrichment (EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease (AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and AD mice. AIM: To study the additive therapeutic effect of EE combined with MgT (EM) and the potential mechanism underlying the effects. MATERIALS AND METHODS: APP/PS1 mice were treated with EE, MgT, or combination of EE and MgT (EM) and compared for restored memory function. RESULTS: EM was more effective in improving cognition and spatial memory than either treatment alone in either long-term (12 months, started at 3 months old, which was before disease manifestation) or short-term (3 months, started at 6 months old, which was after disease manifestation) treatment. The behavioral improvement has coincided with rescue of synaptic contacts in the hippocampal region of the AD mouse brain. Immunoblots also showed that EM but neither single treatment rescued the activity reduction in CaMKII and CREB, two important downstream molecules in the N-methyl-D-aspartate receptor (NMDAR) pathway. CONCLUSION: Environmental enrichment and MgT may synergistically improve recognition and spatial memory by reducing synaptic loss and restoring the NMDAR signaling pathway in AD mice, which suggests that combination of EE and MgT may be a novel therapeutic strategy for AD.
BACKGROUND: Environmental enrichment (EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease (AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and ADmice. AIM: To study the additive therapeutic effect of EE combined with MgT (EM) and the potential mechanism underlying the effects. MATERIALS AND METHODS: APP/PS1mice were treated with EE, MgT, or combination of EE and MgT (EM) and compared for restored memory function. RESULTS:EM was more effective in improving cognition and spatial memory than either treatment alone in either long-term (12 months, started at 3 months old, which was before disease manifestation) or short-term (3 months, started at 6 months old, which was after disease manifestation) treatment. The behavioral improvement has coincided with rescue of synaptic contacts in the hippocampal region of the ADmouse brain. Immunoblots also showed that EM but neither single treatment rescued the activity reduction in CaMKII and CREB, two important downstream molecules in the N-methyl-D-aspartate receptor (NMDAR) pathway. CONCLUSION: Environmental enrichment and MgT may synergistically improve recognition and spatial memory by reducing synaptic loss and restoring the NMDAR signaling pathway in ADmice, which suggests that combination of EE and MgT may be a novel therapeutic strategy for AD.
Authors: S Sinha; J P Anderson; R Barbour; G S Basi; R Caccavello; D Davis; M Doan; H F Dovey; N Frigon; J Hong; K Jacobson-Croak; N Jewett; P Keim; J Knops; I Lieberburg; M Power; H Tan; G Tatsuno; J Tung; D Schenk; P Seubert; S M Suomensaari; S Wang; D Walker; J Zhao; L McConlogue; V John Journal: Nature Date: 1999-12-02 Impact factor: 49.962
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