СЕРОТОНИНЕРГИЧЕСКИЕ НЕРВЫ И ПОДТИПЫ ИХ РЕЦЕПТОРОВ

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