СЕРОТОНИНЕРГИЧЕСКИЕ НЕРВЫ И ПОДТИПЫ ИХ РЕЦЕПТОРОВ
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alternative, non-native amyloid self-assemblies including amyloid oligomers and fibrils which may be delivered in vivo by the nasal vector (Gruden et al., 2013). Accordingly, synthetically generated toxic oligomers or fibrils were administered intranasally to mice for 14 days and “open-field” behavior was subsequently tested on days 0 and 14 days after treatment completion. Behavioral deficits at the end of the dosing regime and 14 days later included rigidity, hypokinesia and immobility. This was accompanied by elevated DA, DOPAC and HVA concentrations only in the substantia nigra (SN) in response to dual administration of α-syn oligomers plus fibrils but not the oligomers by themselves. α-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the SN. Only nigral DA turnover (DOPAC/DA) but not HVA/DA ratios were augmented in response to fibril treatment but there were no changes in the striatum. The α-syn oligomer/fibril mixture instigated PD-like motor symptoms which also correlated heterochronically with elevated NA levels in the striatum but then later in the SN intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations in the protocol (Gruden et al., 2015). In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Amyloid seeding plus neurodegenerative apoptotic pores as well as actions on neurotransmitter synthesis and/or transporters (such as NET, SERT and VMAT2) are potentially implicated in these α-syn amyloid induced neurochemical and motoric disturbances. In addition, activation of the immune system towards misfolded α-syn species and dopamine occurred during the experimental protocol in the mice. Compilation of these novel behavioral, immunological and neurochemical findings substantiate the validity of the α-syn nasal vector model for investigating parkinsonian-like symptoms. References 1. Gruden MA, Sewell RDE, Yanamandra, K, Davidova TV, Kucheryanu, VG, Bocharov EV, Bocharova OR, Polyschuk VV, Sherstnev VV, Morozova-Roche LA. Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression. J Neuroimmunol. 2011;233:221-227. 2. Gruden M A, Davidova T V, Yanamandra K, Kucheryanu V G, Morozova Roche LA, Sherstnev VV, Sewell RDE. Nasal inoculation with α-synuclein aggregates evokes rigidity, locomotor deficits and immunity to such misfolded species as well as dopamine. Behav Brain Res. 2013;243:20512. 3. Gruden MA, Davydova TV, Narkevich VB, Fomina VG, Wang C, Kudrin VS, Morozova-Roche LA, Sewell RD. Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms. Behav Brain Res. 2015 Feb 15;279:191-201. doi: 10.1016/j.bbr.2014.11.001. DOI:10.12737/12272 СЕРОТОНИНЕРГИЧЕСКИЕ НЕРВЫ И ПОДТИПЫ ИХ РЕЦЕПТОРОВ Смирнов В.М., Свешников Д.С., Мясников И.Л., Кучук А.В. Российский университет дружбы народов, Москва