Delayed effects of combined stress and Aβ infusion on L-LTP of the dentate gyrus: Prevention by nicotine.

Alzheimer's Disease (AD) is a progressive dementia hallmarked by the presence in the brain of extracellular beta-amyloid (Aβ) plaques and intraneuronal fibrillary tangles. Chronic stress is associated with heightened Aβ buildup and acceleration of development of AD, however, stress alone has no significant effect on synaptic plasticity in the dentate gyrus (DG) area. Previously, we have reported that the combination of stress and AD causes more severe inhibition of synaptic plasticity of hippocampal area CA1 than chronic stress or AD alone, and that chronic nicotine treatment prevents this impairment. To investigate the effect of stress and nicotine on synaptic plasticity in the relatively injury-resistant DG area, the present experiments analyzed the effect of chronic stress and the neuroprotective effect of nicotine on LTP in the DG area of a rat model of AD. Wistar rats were chronically stressed and treated with nicotine (1 mg/kg/twice daily; s.c.) for six weeks. Then, at weeks 5-6, AD model was generated by 14-day i.c.v osmotic pump infusion of Aβ peptides (300 pmol/day) into the brains of these rats. Field potential recordings from the DG area of anesthetized rats, revealed that while chronic stress did not accentuate Aβ-induced impairments of E-LTP, it markedly augmented Aβ effect on L-LTP that was only seen 100 min after multiple high frequency stimulation. This delayed action is likely to be due to impairment of process of de novo protein synthesis required for maintenance phase of L-LTP. Chronic nicotine treatment prevented stress-enhanced suppression of synaptic plasticity.