Anti-Oxidative Stress Activity Is Essential for Amanita caesarea Mediated Neuroprotection on Glutamate-Induced Apoptotic HT22 Cells and an Alzheimer's Disease Mouse Model

Int J Mol Sci. 2017 Jul 27;18(8):1623. doi: 10.3390/ijms18081623.

Abstract

Amanita caesarea, an edible mushroom found mainly in Asia and southern Europe, has been reported to show good antioxidative activities. In the present study, the neuroprotective effects of A. caesarea aqueous extract (AC) were determined in an l-glutamic acid (l-Glu) induced HT22 cell apoptosis model, and in a d-galactose (d-gal) and AlCl₃-developed experimental Alzheimer's disease (AD) mouse model. In 25 mM of l-Glu-damaged HT22 cells, a 3-h pretreatment with AC strongly improved cell viability, reduced the proportion of apoptotic cells, restored mitochondrial function, inhibited the over-production of intracellular reactive oxygen species (ROS) and Ca2+, and suppressed the high expression levels of cleaved-caspase-3, calpain 1, apoptosis-inducing factor (AIF) and Bax. Compared with HT22 exposed only to l-Glu cells, AC enhanced the phosphorylation activities of protein kinase B (Akt) and the mammalian target of rapamycin (mTOR), and suppressed the phosphorylation activities of phosphatase and tensin homolog deleted on chromosome ten (PTEN). In the experimental AD mouse, 28-day AC administration at doses of 250, 500, and 1000 mg/kg/day strongly enhanced vertical movements and locomotor activities, increased the endurance time in the rotarod test, and decreased the escape latency time in the Morris water maze test. AC also alleviated the deposition of amyloid beta (Aβ) in the brain and improved the central cholinergic system function, as indicated by an increase acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations and a reduction in acetylcholine esterase (AchE) levels. Moreover, AC reduced ROS levels and enhanced superoxide dismutase (SOD) levels in the brain of experimental AD mice. Taken together, our data provide experimental evidence that A. caesarea may serve as potential food for treating or preventing neurodegenerative diseases.

Keywords: Alzheimer’s disease; Amanita caesarea; apoptosis; cholinergic transmitters; oxidative stress.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase / blood
  • Aluminum Chloride
  • Aluminum Compounds
  • Alzheimer Disease / blood
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Amanita / chemistry*
  • Amyloid beta-Peptides / blood
  • Animals
  • Apoptosis / drug effects*
  • Brain / enzymology
  • Brain / pathology
  • Cell Line
  • Chlorides
  • Choline O-Acetyltransferase / blood
  • Disease Models, Animal
  • Galactose
  • Glutamic Acid / toxicity*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroprotection* / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidation-Reduction
  • Oxidative Stress* / drug effects
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Aluminum Compounds
  • Amyloid beta-Peptides
  • Chlorides
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Aluminum Chloride
  • Glutamic Acid
  • Superoxide Dismutase
  • Choline O-Acetyltransferase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Acetylcholinesterase
  • Acetylcholine
  • Galactose