Effect of memantine on expression of Bace1-as and Bace1 genes in STZ-induced Alzheimeric rats

Mol Biol Rep. 2020 Aug;47(8):5737-5745. doi: 10.1007/s11033-020-05629-7. Epub 2020 Jul 9.

Abstract

Recent studies have showed that the long non-coding RNAs (lncRNAs) expression is dysregulated in different neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the effects of memantine on the level of Bace1-as and Bace1 genes' expression in streptozotocin (STZ)-induced Alzheimer's and memantine treated rats were investigated. The male Wistar rats were randomly divided into four groups: 1-Normal control, 2-Sham-operated control, 3- Alzheimer'scontrol rats (ICV-STZ), 4-Experimental group rats treated by memantine in a dose of 30 mg/kg/day for 28 days in ICV-STZ rats. The expression of Bace1-as and Bace1 genes was measured by quantitative-PCR in the brain and blood tissues. ELISA was used to analyze Bace1 and Aβ proteins. Expression of Bace1-as was significantly increased in the brain and blood tissues of the experimental group (p = 0.032 and p = 0.034, respectively). The expression of Bace1 gene showed no significant changes in the brain. Furthermore, the ELISA analysis revealed that Bace1 protein was significantly increased in the plasma of the Alzheimer's control group (p = 0.000) and in the brain tissue of the experimental group (p = 0.000). Additionally, Aβ levels had no significant changes between all groups studied. The Bace1 protein may be used as a prognostic biomarker in plasma, or before using memantine as a treatment. Furthermore, Bace1-as gene expression may play a role in monitoring the progression of AD.

Keywords: Alzheimer’s disease; Bace1 gene; Bace1-as lncRNA; Memantine; Plasma biomarker; Rat; STZ.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases / biosynthesis*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antiparkinson Agents / pharmacology
  • Aspartic Acid Endopeptidases / biosynthesis*
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Maze Learning / drug effects
  • Memantine / pharmacology*
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Streptozocin / administration & dosage

Substances

  • Amyloid beta-Peptides
  • Antiparkinson Agents
  • Biomarkers
  • RNA, Long Noncoding
  • Streptozocin
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, rat
  • Memantine