Expression of NLRP3 Inflammasomes in Neurogenic Niche Contributes to the Effect of Spatial Learning in Physiological Conditions but Not in Alzheimer's Type Neurodegeneration.

A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aß1-42). We found that in Aß-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aß injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer's type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.

[The battery of tests for behavioral phenotyping of aging animals in the experiment].

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

Log-log growth of channel capacity for nondispersive nonlinear optical fiber channel in intermediate power range: Extension of the model.

In our previous paper [Terekhov et al., Phys. Rev. E 95, 062133 (2017)2470-004510.1103/PhysRevE.95.062133] we considered the optical channel modeled by the nonlinear Schrödinger equation with zero dispersion and additive Gaussian noise. We found per-sample channel capacity for this model. In the present paper we extend the per-sample channel model by introducing the initial signal dependence on time and the output signal detection procedure. The proposed model is a closer approximation of the realistic communications link than the per-sample model where there is no dependence of the initial signal on time. For the proposed model we found the correlators of the output signal both analytically and numerically. Using these correlators we built the conditional probability density function. Then we calculated an entropy of the output signal, a conditional entropy, and the mutual information. Maximizing the mutual information we found the optimal input signal distribution, channel capacity, and their dependence on the shape of the initial signal in the time domain for the intermediate power range.

[Early changes in hyppocampal neurogenesis induced by soluble Ab1-42 oligomers]. / Rannie izmeneniia v gippokampal'nom neirogeneze, indutsirovannye rastvorimymi formami oligomerov Ab1-42.

Alzheimer's disease is characterized by the loss of neurons, the accumulation of intracellular neurofibrillary tangles and extracellular amyloid plaques in the brain. However, there are contradicting data on differences in neurogenesis at the onset of the disease or before the formation of amyloid plaques. As awareness of the importance of the pre-symptom phase in neurodegenerative diseases grows in the context of early diagnosis and pathogenesis, we analyzed the critical periods of adult hippocampal neurogenesis at an early stage under the action of soluble Ab1-42 beta-amyloid. The proliferation, migration and neuronal cells survival were evaluated in mice with an injection of soluble amyloid beta-oligomers. It was found that the injection of Ab1-42 oligomers causes a decrease in cell proliferation in the mouse hippocampus. Despite the preservation of the neuroblast pool in animals after beta-amyloid injection, the process of radial migration is disrupted, and an increase in apoptosis in the neurogenic niche was revealed. Thus, our results demonstrate damage of neurogenesis critical stages: the progenitor cells, neuroblast migration, the integration of immature neurons, and the survival of neurons under application of soluble beta-amyloid oligomers. The obtained data indicate decline in proliferation rate in the subgranular zone, that is accompanied by ectopic differentiation and disturbed migration, producing, apparently, abnormal neurons that have lower survival rates. That could lead to a decrease in mature neurons numbers and the number of cells in the granular layer of the dentate gyrus.

Large negative velocity gradients in Burgers turbulence.

We consider one-dimensional Burgers equation driven by large-scale white-in-time random force. The tails of the velocity gradients probability distribution function (PDF) are analyzed by saddle point approximation in the path integral describing the velocity statistics. The structure of the saddle-point (instanton), that is, the velocity field configuration realizing the maximum of probability, is studied numerically in details. The numerical results allow us to find analytical solution for the long-time part of the instanton. Its careful analysis confirms the result of Balkovsky et al. [Phys. Rev. Lett. 78, 1452 (1997)] based on short-time estimations that the left tail of PDF has the form ln P(u(x))infinity-/u(x)/(3/2).

[Study of antigenic structure of HIV-1 protein p24 using monoclonal antibodies]. / Izuchenie antigennoi struktury belka p24 VICh-1 s pomoshch'iu monoklonal'nykh antitel.

During the experiments 4 murine and 3 rat hybridomas producing monoclonal antibodies (MAb) against the protein p24 of human immunodeficiency virus type 1 (HIV-1) have been obtained. Using the immunoblotting technique, it was established that all the species of MAb reacted with the same viral proteins which are derivatives of gag gene--p24 and p55. The properties of MAb have been studied in competitive binding. Their ability of binding to different fragments of the gag protein produced by the recombinant plasmids in E. coli cells have been investigated in ELISA. The analysis of the findings suggests that the HIV-1 protein p24 contains at least 3 antigenic epitopes. All species of MAb reacted with 3 different HIV-1 strains and 2 HIV-1 isolates, but failed with 2 different HIV-2 strains. The only MAb NS5E4 can be used as an immunosorbent in the antigenic capture reaction.