Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease

Chennakesavan Karthick, Saravanan Nithiyanandan, Musthafa Mohamed Essa, Gilles J. Guillemin, Swaminathan K. Jayachandran, Muthuswamy Anusuyadevi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aβ) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aβ influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aβ(1–42) (oAβ1–42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. Methods: Aggregated forms of synthetic Aβ peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription–polymerase chain reaction. Results: oAβ1–42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAβ1–42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-β1–42 are highly expressed in 15 days after postinjection in hippocampus of adult rats. Conclusion: Acute exposure of oAβ1–42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments.

Original languageEnglish
Pages (from-to)139-150
Number of pages12
JournalNeurological Research
Issue number2
Early online date19 Nov 2018
Publication statusPublished - Feb 2019


  • acetylcholine receptor
  • Alzheimer’s disease
  • amyloid-β
  • hippocampus
  • NMDA receptor
  • spatial learning and memory

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