Neuroprotective effects of hydrated fullerene C60: cortical and hippocampal EEG interplay in an amyloid-infused rat model of Alzheimer's disease.

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-ß (Aß) rat model of Alzheimer's disease (AD). Infusion of Aß1-42 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 Aß1-42 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 Aß transformation in different ways. To clarify its role in the cortex-hippocampus interplay in the Aß 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 Aß1-42 alone, APO attenuated the cortical beta predominance, with immediate and delayed phases evident in the Aß1-42-rats. Pretreatment with C60HyFn diminished the APO effect in the Aß1-42-treated rats. Thus, we show that intrahippocampal injection of Aß1-42 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.

Effects of nootropics on the EEG in conscious rats and their modification by glutamatergic inhibitors.

To study the effects of acute and repeated injections of nootropics and to learn how glutamate receptors might be involved in their mediation, the frequency spectra of cortical and hippocampal electroencephalogram (EEG) were analyzed in non-narcotized rats subcutaneously injected repeatedly with Piracetam (400mg/kg) or its analogue, Noopept (0.2mg/kg), after intracerebroventricular infusions of saline (5 µl) or the antagonists of NMDA and quisqualate/AMPA receptors: CPP (0.1 nmol) and GDEE (1 µmol), respectively. Piracetam increased alpha/beta1 EEG activity in the left frontal cortex, and alpha activity in both the right cortex and hippocampus, with a 10-min latency and 40-min duration. Noopept increased alpha/beta1 activity, with 30-min latency and 40-min duration in all brain areas. CPP pretreatment eliminated Piracetam EEG effects; reduced Noopept effects in the cortex and completely suppressed them in the hippocampus. After four injections of Piracetam, EEG effects were very small in the cortex, and completely lacking in the hippocampus, while GDEE pretreatment partially recovered them. The effect of Noopept in the alpha/beta1 ranges was replaced by increased beta2 activity after the eighth injection, while no effects were observed after the ninth one. GDEE pretreatment restored the effect of Noopept in the beta2 frequency range. These results demonstrate similarities in EEG effects and their mediatory mechanisms for Piracetam and its much more effective analogue, Noopept. Activation of NMDA receptors is involved in the effects of a single injection of the nootropics, whereas activation of quisqualate/AMPA receptors is associated with the decrease in their efficacy after repeated use.

Cortical and hippocampal EEG effects of neurotransmitter agonists in spontaneously hypertensive vs. kainate-treated rats.

To analyze mediatory mechanisms underlying attention-deficit hyperactivity disorder (ADHD) and their association with epilepsy, the electroencephalogram (EEG) responses to various centrally applied neurotransmitter agonists were studied in spontaneously hypertensive (SH), kainate-treated (KA), and normotensive (control) rats, with chronically implanted electrodes into the frontal cortex and hippocampus and a cannula into the lateral cerebral ventricle. In SH rats, the baseline EEG showed increased delta and beta2 activity in the hippocampus and decreased alpha/beta1 activity in both brain areas. In KA rats, these delta and alpha/beta1 effects were observed 2 weeks post-kainate, while the beta2 activity increase occurred after 5 weeks in the hippocampus and, to a greater extent, 9 weeks post-injection in both brain areas. In SH rats, NMDA increased delta and decreased alpha/beta1 activity, similar to KA rats 5 weeks post-injection. In SH rats, clonidine augmented theta/beta2 increase in the cortex and alpha suppression in both brain areas, in parallel with induction of beta2 activity in the hippocampus. These beta2 effects were observed 5 and 9 weeks post-kainate. In SH rats, baclofen produced robust delta/theta enhancement and alpha/beta1 suppression in both brain areas, with additional beta2 activity increase in the hippocampus, while muscimol was ineffective in both groups of rats. In KA rats, EEG responses to GABA agonists were similar to those in control. Our results demonstrate sensitization of NMDA receptors and α2-adrenoceptors both in SH and KA rats and that of GABAb receptors specifically in SH rats.