ROLE OF PRO-INFLAMMATORY S100 PROTEINS IN AMYLOID DISEASES

dopamine receptors (D1, 1:200) were used. The optical density (OD, in 
arbitrary units)  of THf40 and THf31 was determined  in  images of 
dopaminergic neurons of the substantia nigra (SN) and the ventral 
tegmental area (VTA).  Statistical analysis was performed using t-test. 
Results are presented as mean ± standard error and in percents. The 
double 
immunohistochemical reaction was performed on midbrain area 

sections.  The primary rabbit antibodies to the phosphorylated protein 
kinase-A (fPKA, Abcam, UK; 1: 100) and mouse to the TH (Sigma, USA, 1: 
1000) were used as previously described [3] and studied by confocal 
microscopy (Leika XP5).
RESULTS
In Ay /a mice in obesity and decrease the level of AgRP in brain 
dopaminergic neurons in the arcuate nucleus, zona incerta, substantia 
nigra, ventral tegmental area the OD of  THf40 was increased on 25-30% 
compared to a/a mice. Significant differences of  THf31 OD in 
dopaminergic neurons and in areas of dopamine innervation was not 
detected. 
The 
double 
immunolabeling 
indicated 
 
that 
the 

immunoreactivity of  fPKA in dopaminergic neurons in the midbrain 
substantia nigra and ventral tegmental area was increased. In the 
paraventricular nucleus of the hypothalamus, which is well known, 
receives abundant dopaminergic innervation, the immunoreactivity of 
THf40 and D1   have been increase. The data indicate that the 
activation of dopamine biosynthesis systems in obese Ay/a mice occurs 
during G-protein coupled activation interacting messengers. It is 
suggested that the protein agouti, intracellular overexpressed  in Ay/a 
mice, may have an inhibitory effect on ERK-module and associated 
mechanisms.
Research was  supported by RFBR grant №14-04-31565_ mol-a.
LITERATURE
[1] Bagnol  D., Lu X.Y., Kaelin C.B., Day H.E., Ollmann  M., Gantz  I., 
Akil  H., Barsh G.S., Watson  S.J. Anatomy of an Endogenous Antagonist: 
Relationship between Agouti-Related Protein and Proopiomelanocortin in 
Brain.  J. Neurosci. 1999. V. 19.  P. 1-7. 
[2] Makarova, E.N., Yakovleva, T.V., Shevchenko, A.Y. Pregnancy and 
lactation have antiobesity and anti-diabetic effects in Ay/a mice // 
Acta Physiologica.  2010.  V. 198 (2). P. 169-177. 
[3] Mikhrina A. L., Romanova
I. V.  //Neurosci. Behav. Physiology. 

2015, V. 45 (5).  P. 536-541.
[4] Ollmann M.M., Wilson  B.D., Yang  Y.K., Kerns  J.A., Chen Y., Gantz 
I., Barsh  G.S..// Science.  1997. V. 278. P. 135-138. 
[5] Romanova I. V., Mikhrina  A. L.  //Human Physiology.  2013.  V. 39 
(6).
P. 584-589. 

DOI:10.12737/12425

ROLE OF PRO-INFLAMMATORY S100 PROTEINS IN AMYLOID 

DISEASES

Ludmilla A. Morozova-Roche

Department of Medical Biochemistry and Biophysics, Umeå University, 

Umeå, Sweden

Proteins of S100 family, such as S100A6, S100A8 and S100A, play 

critical 
role 
in 
numerous 
cellular 
processes 
including 
cell 

proliferation, differentiation, motility and danger signaling by 
interacting with and modulating activity of target proteins. They are 
also implicated in the numerous disease pathologies and their 
expression level is significantly increased in many types of cancer, 
inflammatory, neurodegenerative and autoimmune diseases. The functional 
diversity of S100 proteins is achieved via multiple assemblies into 
native homo and hetero oligomeric complexes regulated by Ca2+ and Zn2+binding. By using biophysical and biochemical methods, we have 
demonstrated that both in vitro and in vivo S100A6, S100A8 and S100A9 
proteins can form also alternative, non-native amyloid self-assemblies 
including amyloid oligomers and fibrils. We have found that S100A8 and 
S100A9 are involved in amyloid depositsin such seemingly distant and 
unrelated amyloid diseases as corpora amylacea in ageing and cancer 
affected prostate and amyloid plaques in Alzheimer’s brain tissues, 
while S100A6 contributes to amyloid development in amyotrophic lateral 
sclerosis. What all these diseases have in common is concomitant 
inflammation and elevated level of S100 proteins, which can serve as 
prerequisite for their amyloid assembly. The amyloidogenicity of S100s 
is regulated by Ca2+ and Zn2+-binding and effectively competes with the 
formation of their native functional complexes. Apart from forming 
amyloids themselves S100 protein can also modulate the amyloid assembly 
of major amyloid denominators of corresponding diseases. Their high 
intrinsic amyloid propensity may lead to their amyloid depositions in 
other ailments, which still need to be examined, especially if these 
diseases have an increased expression of S100s. The implications for 
therapeutic treatment and diagnostics of the amyloid diseases are 
discussed.
DOI:10.12737/12426

ИССЛЕДОВАНИЕ ДЕЙСТВИЯ МЕЛАТОНИНА НА СИНАПТИЧЕСКУЮ ПЕРЕДАЧУ В

СА1 ОБЛАСТИ ГИППОКАМПА КРЫС

Мотин В.Г., Яснецов В.В.*

ФГБНУ «Научно-исследовательский институт нормальной  физиологии имени 

П.К.Анохина», Москва

*АО «Всероссийский научный центр по безопасности биологически активных 

веществ», Московская область, Ногинский район, г. Старая Купавна

vicyas@yandex.ru, vmotin@hotmail.com

В экспериментах на переживающих
срезах гиппокампа крыс показано, что 

мелатонин в концентрации 0,5 мМ  существенно не изменял популяционные 
ответы, в концентрации 2 мМ угнетал их на 243%, а в 5 мМ – на 726%, 
не 
вызывая 
эпилептиформной 
активности.
Следовательно, 
мелатонин

способен угнетать синаптическую передачу в системе коллатерали Шаффера 
–
пирамидные 
нейроны 
поля 
СА1 
гиппокампа 
крыс, 
не 
вызывая 

эпилептиформной активности; при этом при увеличении концентрации 
мелатонина (от 0,5 до 5 мМ) возрастает его эффект.