Neuroprotective effects of hydrated fullerene C60: 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 Aβ1-42 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 Aβ1-42 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 Aβ1-42 alone, APO attenuated the cortical beta predominance, with immediate and delayed phases evident in the Aβ1-42-rats. Pretreatment with C60HyFn diminished the APO effect in the Aβ1-42-treated rats. Thus, we show that intrahippocampal injection of Aβ1-42 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.