Elaeagnus glabra f. oxyphylla Attenuates Scopolamine-Induced Learning and Memory Impairments in Mice by Improving Cholinergic Transmission via Activation of CREB/NGF Signaling

Nutrients. 2019 May 28;11(6):1205. doi: 10.3390/nu11061205.

Abstract

We aimed to investigate the therapeutic effects of an Elaeagnus glabra f. oxyphylla (EGFO) ethanol extract in mice with scopolamine-induced memory dysfunction. Fifty male mice were randomly divided into a normal control group, a scopolamine-treated group, a scopolamine and EGFO extract-treated group, and a scopolamine and tacrine-treated group. EGFO (50 or 100 mg/kg/day) was received for 21 days. Step-through passive avoidance and Y-maze tests were performed to examine the effects of treatment on learning and memory impairments. Acetylcholine (Ach) levels and acetylcholinesterase (AchE) activity were measured via an enzyme-linked immunosorbent assay (ELISA). Levels of choline acetyltransferase (ChAT), nerve growth factor (NGF), cAMP response element-binding protein (CREB), and apoptosis-related protein expression were determined via Western blot analysis. EGFO pretreatment significantly attenuated scopolamine-induced memory impairments, relative to findings observed in the scopolamine-treated group. Levels of cholinergic factors in the brain tissues were markedly attenuated in the scopolamine-treated group. EGFO treatment also attenuated neural apoptosis in scopolamine-treated mice by decreasing the expression of apoptosis-related proteins such as Bax, Bcl2, cleaved caspase-3, and TUNEL staining. These results suggest that EGFO improves memory and cognition in a mouse model of memory impairment by restoring cholinergic and anti-apoptotic activity, possibly via activation of CREB/NGF signaling.

Keywords: Alzheimer’s disease; cAMP response element-binding protein (CREB); cholinergic system; memory dysfunction; nerve growth factor (NGF); scopolamine.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Cholinergic Fibers / drug effects*
  • Cholinergic Fibers / metabolism
  • Cholinergic Fibers / pathology
  • Cognition / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Disease Models, Animal
  • Elaeagnaceae* / chemistry
  • GPI-Linked Proteins / metabolism
  • Male
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / metabolism
  • Memory Disorders / prevention & control*
  • Memory Disorders / psychology
  • Mice, Inbred ICR
  • Nerve Growth Factor / metabolism*
  • Plant Preparations / isolation & purification
  • Plant Preparations / pharmacology*
  • Scopolamine
  • Synaptic Transmission / drug effects*

Substances

  • Apoptosis Regulatory Proteins
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • GPI-Linked Proteins
  • Plant Preparations
  • Nerve Growth Factor
  • Scopolamine
  • Acetylcholinesterase
  • Ache protein, mouse
  • Acetylcholine