Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model

PLoS One. 2014 Sep 30;9(9):e108645. doi: 10.1371/journal.pone.0108645. eCollection 2014.

Abstract

Alzheimer's disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Animals
  • Cognition / drug effects*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Injections, Intraperitoneal
  • Insulin Resistance
  • Long-Term Potentiation / drug effects*
  • Magnesium Sulfate / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / agonists
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • tau Proteins / antagonists & inhibitors
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Neuroprotective Agents
  • tau Proteins
  • Streptozocin
  • Magnesium Sulfate
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3

Grant support

This work was supported in part by grants from Natural Science Foundation of China (81261120570) and Science and Technology Committee of China (2013DFG32670). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.