Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.

In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-β (Aβ) 25-35-induced murine model of Alzheimer's disease (AD). Aβ-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks.

Comparative analysis of early neurodegeneration signs in a mouse model of Alzheimer's disease-like pathology induced by two types of the central (Intracerebroventricular vs. Intrahippocampal) administration of Aβ oligomers.

Animal models of Alzheimer's disease (AD) induced by intracerebroventricular (ICV) or intrahippocampal (IH) administration of amyloid-beta (Aβ) are widely used in current research. It remains unclear whether these models provide similar outcomes or mimic pathological mechanisms of AD equally. The aim of the work was to compare two models induced by ICV or IH administration of Aβ oligomers to C57BL/6 mice.

Combined induction of mTOR-dependent and mTOR-independent pathways of autophagy activation as an experimental therapy for Alzheimer's disease-like pathology in a mouse model.

Alzheimer's disease (AD) is associated with amyloid-β (Aβ) accumulation that might be hindered by autophagy. There are two ways to induce autophagy: through mTOR-dependent and mTOR-independent pathways (here, by means of rapamycin and trehalose, respectively). The aim of this study was to evaluate the contribution of these pathways and their combination to the treatment of experimental AD.

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties.

Background: The dominant hypothesis about the pathogenesis of Alzheimer's disease (AD) is the "amyloid cascade" concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD. The molecular mechanisms of this effect are not completely clear, we suggested that the drug might serve as the regulator of the expression of the genes involved in the metabolism of Aβ and the pathogenesis of AD.

[The tissue oxygen partial pressure in organs of hens in the second half of embryogenesis and in the first days after hatching].

The aim of the study was measure the development chick tissue partial pressure of oxygen (pO2) in the brain cerebral hemispheres, liver, M. pectoralis, M. gastrocnemius, and to estimate the correlation of this index with our previously measured values (laser-Doppler flowmetry) volume blood flow (BF) in these organs.

[Aorta, pulmonary artery, and blood flows on them in chickens in the second half of embryogenesis and after hatching].

The aim of the study was to determine changes in the blood flow in arterial trunks (coming out of the heart of chickens) by changes of the lumen of these arteries during embryogenesis (on the 10th, 15th, and 19th days) and 6 days after the hatching. For this purpose, posthumous morphometry of aorta, pulmonary arteries, and arterial (Botallo's) ducts (AD) from their exit from the heart until final extraorgan branching was conducted. It was demonstrated that, in this period, (1) initial lumens of aorta and pulmonary arteries are equal to each other and are equally increased (with temporary stop in last quarter of embryogenesis) with an increase of the body weight (BW); (2) the portion of the right ventricle in a total blood circulation minute volume (BCMV) is somewhat smaller than the portion of the left ventricle, but it approaches equality to it by the end of embryogenesis; (3) with the growth of embryos, the portion of total BCMV flowing through the anterior (before the inflow of AD into the aorta) part of the body decreases; that in the average part increases (from 17 to 31%); that in the posterior part (after bifurcation of aorta), where chorioallantoic membrane (CAM) is located, remains almost unchanged; (4) after the hatching (and disappearance of CAM), BCMV of the left ventricle multiply increases due to the junction of two blood flows from the heart (through the ascending aorta and AD) into a single flow, which flows sequentially by lesser and greater circulations, resulting in multiple increase in the organ blood flow.

[Reactivity of microvessels in the cerebral hemispheres and the skeletal muscles in chicken during second half of embryogenesis].

At Leghorn hens in the second half of embryogenesis and in 4-day-old chicks are studied reaction volume flow velocity (VF) in the superficial layers of the cerebral hemispheres and in skeletal muscle (Lazer Doppler FIowmetry) after the local influence of norepinephrine and sodium nitroprusside. It is shown that the response to these substances begins to manifest itself in the hemisphere in the last quarter of embryogenesis and authentically expressed by the end of it and in the chickens. It is noted that the response to these substances skeletal muscle VF (according to the new and previously published data on gastrocnemius and pectoral muscle) is also clearly manifested by the end of embryogenesis.

[Quantitative relationship of renal blood flow with size and density of glomeruli in rat postnatal ontogenesis].

The aim of the study was to find the quantitative relationship of postnatal changes in the glomeruli anatomic structure with the blood flow in kidneys. Kidney development was studied in 4-, 12-, 30-, and 65-day-old Wistar rats. Diameters of glomerulus (Dgl, microm), afferent and efferent arterioles (Daf and Def), and the glomeruli density (Ngl, mm(-3)) were measured posthumously.

[Blood flow in the brain and liver of chicken in embryonal and early postembryonal periods].

In chicken Leghorn, blood flow volume speed (BF, laser-Doppler flowmetry) in the brain hemispheres and in liver was measured on days 10, 14, and 19 of embryogenesis and on day 4 after hatching (in experiments on late embryos and chickens, urethane narcosis was used). It was revealed, that initial BF in investigated organs was 2-fold lower than earlier measured in skeletal muscles. In the liver, low BF remained at all periods, but it grew 5-fold greater after hatching.

[Blood flow in skeletal muscles of chicken in the embryonic and early postembryonic periods].

In chicken Leghorn, blood flow volume speed in pectoralis and gastrocnemius muscles was measured on 15 and 19 day-old embryos and at the 1st and the 10th days alter hatching. It was revealed that in the last quarter of embryogenesis BF in muscles did not vary remaining in both muscles in identical limits. Similar BF parameters in pectoralis and gastrocnemius muscles and their age-dependent dynamics were observed at embryos with the detained development (with the body weight 2-fold less than the norm).

Changes in tissue metalloproteinase inhibitor-1 and matrix metalloproteinases during tumor development and metastasizing in mice.

Tissue inhibitor of matrix metalloproteinases type 1, inhibiting the majority of matrix metalloproteinases, can both suppress and stimulate tumor growth. The concentrations and activities of tissue matrix metalloproteinase inhibitor-1 were measured in C57Bl/6 mice during progression and metastasizing of Lewis lung adenocarcinoma. Activities of matrix metalloproteinases in tumor tissue of mice were lower than in liver and lung tissues of intact animals.

[Dynamics organ blood flow in rats in postnatal ontogenesis].

In the 4-, 13-, 30-, and 65- 90-day-old Wistar rats the voluminous blood flow rate was measured in liver, kidney, small intestine wall, and in the predominantly white gracilis muscle of femur. A LAKK-01 laser-Doppler flowmeter and its cutaneous (for kidney) and needle (for other organs) probes were used; they provided estimation of blood flow (per organ mass unit) to the tissue depth of about 1 mm. It has been found that the blood flow rates (per organ mass unit fall in liver, intestine, and even more in muscle, whereas increase in kidney, particularly for the first month of life.

[Circulatory system in chicken skeletal muscle in the second half of embryogenesis: shape, bloodstream, and vascular reactivity].

A restructuring of the capillary bed-from the embryonic structure with a three-dimensional network of wide and long protocapillaries to the mature structure with high density of thin and short capillaries along the fibers-has been demonstrated in the chick skeletal muscle on embryonic days 10-19 by morphometric analysis. In this case, the volumetric flow rate and capillary luminal area per cm3 of the muscle remained unaltered, while the blood volume in it significantly dropped. The response of muscle circulation to nitroprusside (increase) and noradrenaline (decrease) appeared in 19-day-old embryos, but this response could develop only under conditions of initially low or high bloodstream, respectively.

[The glomerular apparatus and renal blood flow in rats during postnatal ontogenesis].

In anesthetized Wistar rats of the age of 4, 12, 30 and 65 days, the renal blood flow (RBF) with laser-Doppler flowmetry, diameter, number and density of glomeruli, diameter of afferent and efferent arterioles were measured. We found that during rat development the RBF increased 2.8-fold, the diameter of glomeruli--3.

[The muscular blood flow in rats in ontogenesis as measured by the needle probe laser Doppler flowmeter "LAKK-01"].

In anesthetized Wistar rats of the age of 4, 13, 30 and 90 days, blood flow in m. gracilis was measured with the aid of laser-Doppler flowmeter "LAKK-01" with a needle probe. The sharpest postnatal falling of a muscular blood flow was revealed in the first month of life.

[Allometric dependences of oxygen transport parameters in skeletal muscles during ontogenesis of domestic fowl].

In domestic fowl, from day 10 of embryogenesis to six month of postnatal life, investigation into the white glycolytic pectoral and red oxidative gastrocnemius muscles allometric dependences of the structural and functional parameters providing muscular fibres by oxygen: speed of breath of an isolated muscular fibre, size of a surface of an external membrane of mitochondria in a fibre, its permeability to oxygen, density of the capillaries located around of a fibre and in all muscle, volumetric speed of a muscular blood flow, and connection of speed of breath of muscular fibres with weight of a body of a bird.

Using intravascular autoradiography for an estimation of proliferative activity of rat mesenteric microvessel endothelial cells during the first month of postnatal development.

Background/methods: We applied a novel method for studying endothelial cells (EC) by using autoradiography of cells labeled by 3H-thymidine: photo emulsion was administered into the vascular bed. In the flat transparent organ, this method allows to compare the mitotic activity of endothelium (MAE) depending on vessel diameter and animal age.

Results: The number of the labeled ECs in animals was found to be almost equal in all vessels at the same age.

[Development of the mitochondrial apparatus and blood supply of skeletal muscle fibers during ontogenesis of domestic fowl].

The diameter, length, and numerical density of capillaries, diameter of muscle fibers, size and numerical density of their profiles, and relative volume of mitochondria in them were determined in the chicken red oxidative gastrocnemius and white glycolytic pectoral muscle during development from day 10 of embryogenesis to six month of postnatal life. The bulk blood flow was measured in these muscles by hydrogen clearance during postembryonic development. During embryogenesis, the fibers of gastrocnemius muscle develop and grow at a higher rate, while during postembryonic development, those of the pectoral muscle develop faster.

Mitochondria and blood supply of chicken skeletal muscle fibers in ontogenesis.

Skeletal muscles have been studied during ontogenesis to reveal morphological and functional parameters that at most influence the formation of muscles with different levels of oxygen consumption. Development of oxidative red gastrocnemius muscle (RGM) and glycolytic white pectoralis muscle (WPM) has been studied at a period from being 10-day-old chicken embryos until they become 6-month-old chickens. By morphometry, we measured diameter, length, and numerical density of capillaries; muscle fibers diameter; as well as mitochondria's size, density, and volume fraction in muscle fibers.

[Mechanisms of changes in blood flow distribution between organs in hens during ontogenesis].

Anatomical and histological investigations of large arteries feeding head, extremities and chorioallantoic membrane were carried out in 11-, 14-, and 18-day old chicken embryos and in 1- and 40-day old Shaver chickens. The numerical relationships between an arterial diameter and a body mass; a vessel length, its external diameter and a wall thickness, were determined. Our data demonstrate that walls of large arteries in the anterior and the posterior parts of the chicken embryo body are different in quantity, composition, and maturity of their tissue components, determining the lumen size and hemodynamic conditions in the blood bed.

[Coefficient of oxygen diffusion in fibers of the skeletal muscles].

The effective coefficient of oxygen diffusion in muscle fibers (DO2eff) calculated from measured values of O2 critical pressure, O2 intake and fiber diameter in different skeletal muscles in vertebrates turned to be equal to (0.9-1.8) x 10(-6) cm2/s, which is 11 to 33 times lower than O2 in water.

Oxygen diffusion coefficient in isolated chicken red and white skeletal muscle fibers in ontogenesis.

Oxygen diffusion from medium to cultured isolated muscle fibers from red gastrocnemius muscle (deep part) (RGM) and white pectoralis muscle (WPM) of embryonic and postnatal chickens (about 6 months) was explored. The intracellular effective O(2) diffusion coefficient (D(i)) in muscle fiber was calculated from a model of a cylindrical fiber with a uniform distribution of an oxygen sink based on these experimentally measured parameters: critical tension of O(2) (PO(2)) on the surface of a fiber, specific rate of O(2) consumption by a weight unit of muscle fibers (;VO(2)), and average diameter of muscle fibers. The results document the rapid hypertrophic growth of RGM fibers when compared to WPM fibers in the second half of the embryonic period and the higher values of;VO(2) and critical PO(2) during the ontogenetic period under study.