Estradiol prevents Aβ 25 35-inhibited long-term potentiation induction through enhancing survival of newborn neurons in the dentate gyrus

Int J Neurosci. 2016;126(2):154-62. doi: 10.3109/00207454.2014.995267. Epub 2015 May 22.

Abstract

Aim and methods: Estradiol (E2) is reported to attenuate β-amyloid (Aβ) accumulation and slow the progression of Alzheimer's disease (AD). This study explored the beneficial effect of E2 in AD using histological examination and electrophysiological recording technique in AD model mice created by intracerebroventricular injection of β-amyloid 25-35 (Aβ 25-35).

Results: Infusion of Aβ 25-35 reduced the number of newborn neurons in the 2nd week after birth, a critical period for neurite growth, and impaired high-frequency stimulation-dependent long-term potentiation (LTP) induction in perforant path-granular synapses of hippocampal dentate gyrus (DG). Administration of E2 from the 2nd to 4th week after cell birth in Aβ 25-35-mice ameliorated the impairment of newborn neurons and LTP induction in DG. Acute application of E2 failed to increase the newborn neurons and rescue LTP induction in the DG of Aβ 25-35-mice.

Conclusions: The effect of E2 in Aβ 25-35-impaired LTP induction depends on its neuroprotection improvement.

Keywords: estradiol (E2); hippocampus; long-term potentiation (LTP); neurogenesis; β-amyloid (Aβ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Survival / drug effects
  • Dentate Gyrus / cytology*
  • Doublecortin Domain Proteins
  • Electric Stimulation
  • Estradiol / pharmacology*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / drug effects*
  • Neurons / drug effects*
  • Neuropeptides / metabolism
  • Neuroprotective Agents / pharmacology*
  • Patch-Clamp Techniques
  • Peptide Fragments / toxicity*
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • Estradiol
  • Bromodeoxyuridine