Open AccessMagnesium boosts the memory restorative effect of environmental enrichment in Alzheimer's disease mice
Author(s) -
Huang Ying,
Huang Xian,
Zhang Ling,
Han Fang,
Pang KeLiang,
Li Xue,
Shen JianYing
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12775
Subject(s) - environmental enrichment , hippocampal formation , neuroscience , therapeutic effect , disease , creb , nmda receptor , cognition , medicine , hippocampus , alzheimer's disease , pharmacology , receptor , psychology , chemistry , biochemistry , transcription factor , gene
Summary 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 / PS 1 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 Ca MKII 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 .