Magnesium boosts the memory restorative effect of environmental enrichment in Alzheimer's disease mice

SummaryBackground 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.