Tag Archives: brain

Vitamin D(3) auto-/paracrine system in rat brain relating to vitamin D(3) status in experimental type 2 diabetes mellitus

I. Shymanskyi1*, O. Lisakovska1, A. Khomenko1,
L. Yanitska2, M. Veliky1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine;
2Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: ihorshym@gmail.com

Received: 29 January 2024; Revised: 08 March 2024;
Accepted: 11 March 2024; Available on-line: 30 April 2024

Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM.

Nobel prize winners Arvid Carlsson, Paul Greengard and Eric Kandel: the research of signal transduction in the nervous system

T. V. Danylova1,2*, S. V. Komisarenko3

1Institute of Social and Political Psychology, National Academy
of Educational Sciences of Ukraine, Kyiv;
2The Graduate School for Social Research, Institute of Philosophy
and Sociology of the Polish Academy of Sciences,Warsaw, Poland;
*e-mail: danilova_tv@ukr.net;
3Palladin Institute of Biochemistry, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: svk@biochem.kiev.ua

Received: 08 March 2023 2022; Revised: 11 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023

For many decades, scientists have tried to unravel the mysteries of the nervous system – the complex phenomenon that receives messages, processes information, and sends signals to the rest of the body. The most important scientific discoveries of the 19th and the 20th centuries paved the way for the 2000 Nobel Prize in Physiology or Medicine awarded to Arvid Carlsson, Paul Greengard and Eric Kandel “for their discoveries concerning signal transduction in the nervous system”. So, the beginning of the new millennium was “marked” by pioneering research into the chemical transmission of signals in the central nervous system, which created the foundation for a deeper understanding of the mediatory role of dopamine, the processes of slow synaptic transmission, short-term and long-term memory, and the mechanisms of action of antipsychotic and antidepressant drugs. The paper aims to outline the main stages of scientific activities of a Swedish neuropharmacologist Per Arvid Emil Carlsson and the American neurobiologists Paul Greengard and Eric Richard Kandel.

ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study

O. V. Akopova*, L. I. Kolchinskaya, V. I. Nosar,
A. N. Smirnov, L. V. Bratus

Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ov_akopova@ukr.net

Received: 17 January 2020; Accepted: 25 June 2020

The aspects of ATP-sensitive K+ transport regulation by mitochondrial K+,ATP-sensitive (mKATP) channels openers are important for understanding the properties of these channels. The effect of KATP channels openers (KCOs) diazoxide and pinacidil on ATP-sensitive K+ transport in isolated brain mitochondria was studied in the absence and the presence of MgATP using light scattering technique. Without MgATP we observed high sensitivity of ATP-sensitive K+ transport to both drugs with full activation at ≤ 0.5 µM. ATP-sensitive K+ transport was specifically blocked by ATP in the presence of Mg2+. Neither Mg2+ nor ATP affected Vmax of ATP-sensitive K+ transport activated by KCOs, but MgATP shifted the activation curve to micromolar scale. The blockage of ATP-sensitive K+ transport by KATP channels blockers glibenclamide and 5-hydroxydecanoate in the absence and the presence of MgATP proved the sensitivity of ATP-sensitive K+ transport to the blockers of mKATP channel. Full activation of mKATP channel by diazoxide and pinacidil on sub-micromolar scale in the absence of MgATP was shown. The sensitivity of ATP-sensitive K+ transport to the known modulators of mKATP channel (diazoxide, pinacidil, glibenclamide, 5-HD and MgATP) proved the identity of ATP-sensitive K+ transport with mKATP channel activity. Based on our studies, we hypothesized that mKATP channel might comprise high affinity sites for KCOs binding screened by MgATP. The results of this work reveal novel not described earlier aspects of the regulation of ATP-sensitive K+ transport by mKATP channels openers, important for understanding of mKATP channel properties.

Corvitin restores metallothionein and glial fibrillary acidic protein levels in rat brain affected by pituitrin-izadrin

H. N. Shiyntum1, O. O. Dovban1, Y. P. Kovalchuk1,
T. Ya. Yaroshenko2, G. A. Ushakova1

1Oles Honchar Dnipro National University, Ukraine;
2I. Horbachevsky Ternopil State Medical University, Ukraine;
e-mail: hnkafor@yahoo.com

In this research, we investigated the effect of pituitrin-izadrin induced injury on the levels of metallothionein (MT) and soluble and filament forms of glial fibrillary acidic protein (GFAP) in the hippocampus, cerebellum, thalamus, and the cerebral cortex, and examined the effect of corvitin on the brain under the noted changes. Our results showed oppositely directed changes – a decrease in the level of MT and an increase in GFAP in the rat brain, with a tendency to astrogliosis development, under the influence of systemic deficiencies in myocardial function. The use of corvitin at a dose of 42 mg/kg for five days after a cardiac attack caused by pituitary-izadrin leads to recovery in the balance of the studied proteins.

Effect of glyphosate on the energy exchange in carp organs

A. A. Zhidenko, E. V. Bіbchuk, E. V. Barbukho

Taras Shevchenko Chernihiv State Pedagogical University, Ukraine;
e-mail: zaa2006@ukr.net

The use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites (aminomethylphosphonic acid) in food for human consumption and pose a threat to health. The effect of these herbicides on the fish organism at the biochemical level has been insufficiently studied. We studied changes in the content of adenine nucleotides, enzyme activity, quantitative indexes of energy metabolism substrates in carp under the action of glyphosate. It has been found that proteins are the major ener­gy substrate under the influence of glyphosate in the liver, brain, white muscle of carp yearlings. Glyphosphate  decreases energy metabolism in the brain of carp and increases it in the white muscles. The growth of activity of catabolic enzymes in the liver under the influence of glyphosate can be attributed to the adaptive remodelling of metabolic pathways for homeostasis and enantiostasis in response to herbicides

Biochemical effects of estrogens in non-reproductive organs

A. S. Mikosha, E. I. Kovzun, N. D. Tronko

State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: asmikosha@gmail.com

Biochemical processes initiated by estrogenic hormones in the organs which are not directly related to reproduction were described in the survey on the basis of literature and the authors’ own studies. The importance of these compounds in the regulation of fundamental biological processes has been established in the last decades. The biochemical mechanisms of realization of estrogen effects may be considered as potential links of pathogenesis for a number of diseases and as targets of their therapy.

Activity and isozyme content of lactate dehydrogenase under long-term oral taurine administration to rats

R. D. Ostapiv1,2, S. L. Humenyuk2, V. V. Manko1

1Ivan Franko National University of Lviv, Ukraine;
2SSRCI of Veterinary Medicinal Products and Feed Additives, Lviv, Ukraine;
e-mail: romostapiv@gmail.com; vvmanko@lnu.edu.ua

The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190–220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel with further staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies.