Neuroprotective Effects of Hydrated Fullerene C 60 : Cortical and Hippocampal EEG Interplay in an Amyloid-Infused Rat Model of Alzheimer's Disease

Abstract

We studied the effects of fullerene C₆₀ nanoparticles, namely hydrated fullerene C₆₀ (C₆₀HyFn), on interrelations between EEG frequency spectra from the frontal cortex and the dorsal hippocampus (CA1) on an amyloid-β (Aβ) rat model of Alzheimer's disease (AD). Infusion of Aβ_1-42 protein (1.5 μl) into the CA1 region two weeks before EEG testing diminished hippocampal theta (3.8–8.4 Hz) predominance and eliminated cortical beta (12.9–26.2 Hz) predominance observed in baseline EEG of rats infused with saline (control) or with C₆₀HyFn alone. In contrast, these Aβ_1-42 effects were abolished in rats pretreated with C₆₀HyFn, 30 min apart. Dopaminergic mediation in AD has been shown to be involved in neuronal plasticity and Aβ transformation in different ways. To clarify its role in the cortex-hippocampus interplay in the Aβ model of AD, we used peripheral injection of a dopamine agonist, apomorphine (APO), at a low dose (0.1 mg/kg). In rats infused with C₆₀HyFn or Aβ_1-42 alone, APO attenuated the cortical beta predominance, with immediate and delayed phases evident in the Aβ_1-42-rats. Pretreatment with C₆₀HyFn diminished the APO effect in the Aβ_1-42-treated rats. Thus, we show that intrahippocampal injection of Aβ_1-42 dramatically disrupts cortical versus hippocampal EEG interrelations and that pretreatment with the fullerene eliminates this abnormality. We suggest that some effects of C₆₀HyFn may be mediated through presynaptic dopamine receptors and that water-soluble C₆₀ fullerenes have a neuroprotective potential.