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Page 12 of 24 Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019

copy numbers per microliter plasma were calculated by qRT-PCR. We identified, validated, and replicated
three differentially expressed circRNAs, which were upregulated in patients with AIS compared with HCs
-9
-9
(circFUNDC1: P = 0.00014; circPDS5B: P = 4.13 × 10 ; circCDC14A: P = 1.86 × 10 ). With an area under the
curve (AUC) of 0.875 corresponding to a specificity of 91% and a sensitivity of 71.5%, the combination
index of these three circRNAs had diagnostic power for stroke. The baseline circRNA levels showed poor
significance, but the change rate in the level of circRNAs within the first seven days of treatment showed
significance in predicting stroke outcomes (AUCs of circFUNDC1, circPDS5B, circCDC14A, and the
overall circRNA set were 0.884, 0.953, 0.943, and 0.960, respectively). The elevation levels of circRNAs after
stroke might be due to increasing levels in lymphocytes and granulocytes. In conclusion, a set of circulating
circRNAs - circFUNDC1, circPDS5B, and circCDC14A - could not only serve as biomarkers for AIS
diagnosis but also be applied in predicting stroke outcomes.

17. Stress-induced changes of NMDA and AMPA receptor expression in the rat brain are
aggravated by neonatal bacterial endotoxin exposure

1,2
2
2
1
Alexander Trofimov , Veronika Nikitina , Maria Zakharova , Anna Kovalenko , Sergey
2,3
Tsykunov , Gleb Beznin , Darya Krytskaya , Alexander Schwarz , Olga Zubareva 2
1
1
1
1 Laboratory of Neurobiology of the Brain Integrative Functions, I.P. Pavlov Department of Physiology, Institute
of Experimental Medicine, St. Petersburg, Russia
2 Laboratory of Molecular Mechanisms of Neuronal Interactions, I.M. Sechenov Institute of Evolutionary
Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia
3 Multidisciplinary Laboratory of Neurobiology, I.M. Sechenov Institute of Evolutionary Physiology and
Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia
Deregulated glutamatergic transmission is known to be implicated in neurological-psychiatric disorders,
including stress-evoked schizophrenia and post-traumatic stress disorder (PTSD). Structural changes of
NMDA and AMPA receptors can affect glutamatergic transmission. These receptors have a heterotetramer
structure: NMDA-Rs consist of obligatory GluN1 subunit and variable GluN2 (a-d) or GluN3 (a and b)
subunits; AMPA-Rs are composed of obligatory GluA2-dimer and a dimer of two other subunits, GluA1,
GluA3, or GluA4. The expression of NMDA-R and AMPA-R subunit genes in regards to vital stress has only
been explored in few studies without investigation of long-term changes, even though this seems important
for understanding the mechanisms of PTSD. Moreover, these disturbances of glutamic receptor subunit
expression are hypothesized to become even more vulnerable to stress effects after early-life immune
challenges. According to the “two-hit” hypothesis, neonatal pro-inflammatory activation (“first hit”) can
affect brain maturation, thus making stressful events later in life (“second hit”) have a more pronounced
negative effect on brain function that can cause severe mental disorders, including schizophrenia.

The present study was aimed at the investigation of NMDA-R and AMPA-R subunit gene expression in the
rat brain in a model of vital stress alone or combined with neonatal lipopolysaccharide exposure.

Two series of experiments were performed: male three-month-old Wistar rats were subjected to stress
associated with contact with a predator (a black-tailed python) for 40 min either without neonatal
manipulation (Study I) or after treatment with lipopolysaccharide (LPS), 25 or 50 µg/kg, i.p., at P15, P18,
and P21 (Study II). qRT-PCR analysis of mRNA expression of NMDA (GluN1, GluN2a, and GluN2b) and