Geraniol improves passive avoidance memory and hippocampal synaptic plasticity deficits in a rat model of Alzheimer's disease

Eur J Pharmacol. 2023 Jul 15:951:175714. doi: 10.1016/j.ejphar.2023.175714. Epub 2023 Apr 11.

Abstract

Alzheimer's disease (AD) is the most progressive and irreversible neurodegenerative disease that leads to synaptic loss and cognitive decline. The present study was designed to evaluate the effects of geraniol (GR), a valuable acyclic monoterpene alcohol, with protective and therapeutic effects, on passive avoidance memory, hippocampal synaptic plasticity, and amyloid-beta (Aβ) plaques formation in an AD rat model induced by intracerebroventricular (ICV) microinjection of Aβ1-40. Seventy male Wistar rats were randomly into sham, control, control-GR (100 mg/kg; P.O. (orally), AD, GR-AD (100 mg/kg; P.O.; pretreatment), AD-GR (100 mg/kg; P.O.; treatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment & treatment). Administration of GR was continued for four consecutive weeks. Training for the passive avoidance test was carried out on the 36th day and a memory retention test was performed 24 h later. On day 38, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, Aβ plaques were identified in the hippocampus by Congo red staining. The results showed that Aβ microinjection increased passive avoidance memory impairment, suppressed of hippocampal LTP induction, and enhanced of Aβ plaque formation in the hippocampus. Interestingly, oral administration of GR improved passive avoidance memory deficit, ameliorated hippocampal LTP impairment, and reduced Aβ plaque accumulation in the Aβ-infused rats. The results suggest that GR mitigates Aβ-induced passive avoidance memory impairment, possibly through alleviation of hippocampal synaptic dysfunction and inhibition of Aβ plaque formation.

Keywords: Alzheimer's disease; Geraniol; Long-term potentiation; Passive avoidance memory; Rat.

MeSH terms

  • Acyclic Monoterpenes / pharmacology
  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Disease Models, Animal
  • Hippocampus
  • Long-Term Potentiation
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Neurodegenerative Diseases*
  • Neuronal Plasticity
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • geraniol
  • Acyclic Monoterpenes
  • Amyloid beta-Peptides
  • Peptide Fragments