V.V. Vorobyov - Dr.Sc. (Biol.), Leading Research Scientist, Institute of Cell Biophysics RAS (Pushchino). E-mail: vorobyovv2@gmail.com B.V. Bakharev - Ph.D. (Phys.-Math.), Senior Research Scientist, Institute of Cell Biophysics RAS (Pushchino). E-mail: boris_baharev@mail.ru N.V. Bobkova - Ph.D. (Biol.), Head of Laboratory, Institute of Cell Biophysics RAS (Pushchino). E-mail: nbobkova@mail.ru

Amyloid-β peptides (Aβ), playing a central role in Alzheimer-s disease (AD), initiate pathological changes in the cortex (Cx) and hippocampus (Hip). Microinjections of Aβ into the Hip revealed similarities of this model to AD. и disruptions of Hip- and Cx-circuitries and their EEG that are associated with dementia typical of AD [1]. We estimated relative differences in frequency spectra EEG of Cx and Hip in rats, intrahippocampally infused with Аβ1-42. We are also interested in the EEG balance between Cx and Hip before and after peripheral injection of a dopamine (DA) -mimetic, apomorphine (APO). Eight Wistar male rats (290-330 g) with chronically implanted electrodes over frontal Cx and dorsal Hip were used. The frequency spectra of EEG in rats, preliminarily (two weeks apart) infused into Hip with Аβ1-42 (2 nmol/µl), were analyzed before and after subcutaneous injection of either saline (control) or APO, at dose of 0.1 mg/kg. All details associated with the experimenting are described in our previous paper [2]. In control rats, averaged EEG frequency spectra showed theta activity dominating in Hip and beta in Cx. In rats, treated with Аβ1-42, these dominations in averaged EEG spectra were eliminated. APO specific effects on these interrelations were revealed after normalisation to baseline EEGs. In rats treated with Аβ1-42, APO inverted the effect in the beta band observed in control animals. APO has been shown to activate presynaptic receptors at low doses [3]. In our study, APO at low dose produced significant suppression of beta dominance in Cx in rats treated with Аβ1-42, with two phases in the time-course of the effect. This might provide additional support for the involvement of presynaptic DA receptors in Аβ1-42-treated rats since immediate and delayed effects of APO at low doses have been shown in previous studies. This work was financially supported by RHSF grant in frame of project № 16 04 00942 «A study of the brain dopaminergic system involvement in mechanisms of Alzheimer-s disease on models of its sporadic and inherited types».

 

1. Goutagny R., Gu N., Cavanagh C., Jackson J., Chabot J.G., Quirion J.G., Krantic S., Williams S. Alterations in hippocampal network oscillations and theta-gamma coupling arise before Aβ overproduction in a mouse model of Alzheimer\'s disease // Eur J. Neurosci. 2013. V. 37(12). P. 1896-1902.
2. Bobkova N., Vorobyov V., Medvinskaya N., Aleksandrova I., Nesterova I. Interhemispheric EEG differences in olfactory bulbectomized rats with different cognitive abilities and brain beta-amyloid levels // Brain Res. 2008. V. 1232. P. 185-194.
3. Tamminga C.A. Partial dopamine agonists in the treatment of psychosis // J.NeuralTransm.2002. V. 109(3). P. 411-420.