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

Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (A beta) 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 A beta influences N-methyl o-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 A beta((1-42)) (oA beta(1-42)) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. Methods: Aggregated forms of synthetic A beta 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: oA beta(1-42) decreased the gene expression level of alpha 7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oA beta(1-42) aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-beta(1-42) are highly expressed in 15 days after postinjection in hippocampus of adult rats. Conclusion: Acute exposure of oA beta(1-42) 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.