Analysis of neurogenesis alterations in the subgranular zone of the hippocampus in a mouse model of Alzheimer's disease

Alchajmerova bolest je progresivno neurodegenerativno oboljenje i najčešći uzrok demencije kod starijih osoba, sa prevalencom dva puta većom u ženskoj populaciji. Jedna od struktura koje najranije bivaju zahvaćene patohistološkim promenama u AB je hipokampus, deo limbičkog sistema koji ima važnu ulogu u procesima učenja i formiranja memorije. Nova istraživanja potvrdila su da se i kod ljudi u subgranularnoj zoni hipokampusa aktivno odvija proces neurogeneze u adultnom periodu. Imajući u vidu činjenicu da novostvoreni neuroni imaju ulogu u procesima učenja i pamćenja, odnosno da utiču na oblikovanje kognicije i ponašanje individue, smatra se da se kognitivni deficit i gubitak pamćenja kod neurodegenerativnih oboljenja može delom pripisati poremećenoj neurogenezi na nivou subgranularne zone hipokampusa. Istraživanja procesa i dinamike adultne neurogeneze u hipokampusu životinja ili osoba obolelih od Alchajmerove bolesti su dala kontradiktorne rezultate. U zavisnosti od eksperimentalnih uslova, kao što su životinjski model Alchajmerove bolesti, starost i pol životinje, kao i markeri kojima se analiziraju ćelijski procesi, rezultati su ukazali kako na smanjenje, tako i na nepromenjen ili čak povećan obim neurogeneze kod animalnih modela i kod pacijenata obolelih od Alchajmerove bolesti. Dosadašnja istraživanja ukazuju na važnu ulogu članova SOXB grupe transkripcionih faktora u brojnim ćelijskim procesima uključenim u neurogenezu tokom embrionalnog i adultnog perioda razvoja, kao što su održavanje multipotentnosti, proliferacije i diferencijacije neuralnih matičnih/prekursornih ćelija. Pored SOXB transkripcionih faktora određeni neurotrofički faktori, kao što je neurotrofički faktor poreklom iz mozga (BDNF), utiču na procese proliferacije i diferencijacije neuralnih matičnih/prekursornih ćelija. Međutim, tačna uloga ovih faktora u nastanku različitih neurorazvojnih i neurodegenerativnih poremećaja nije dovoljno razjašnjena. Imajući u vidu navedeno, cilj ove studije bio je da se utvrdi obrazac uzrasno-zavisnih promena u ekspresiji SOXB transkripcionih faktora u okviru procesa adultne neurogeneze kod jedinki muškog i ženskog pola, kao i da se ispitaju promene u ekspresiji SOXB transkripcionih faktora kod 5xFAD mišjeg modela Alchajmerove bolesti oba pola i različite starosti...Alzheimer's disease is a progressive neurodegenerative disease and the most common cause of dementia in the elderly, with a prevalence of two times higher in the female population. One of the earliest affected structures by pathohistological changes in AB is the hippocampus, a part of the limbic system that plays an important role in the processes of learning and memory formation. New research has confirmed that even in humans the neurogenesis process actively occurs through the adult period in the subgranular zone of the hippocampus. Bearing in mind the fact that newly created neurons play a role in the processes of learning and memory, affecting the cognition and behavior of an individual, cognitive deficit and memory loss in neurodegenerative diseases can be partly attributed to altered neurogenesis at the level of the hippocampal subgranular zone. Analysis of the adult neurogenesis processes in the hippocampus of animals or persons suffering from Alzheimer's disease have resulted in contradictory data. Depending on experimental conditions, such as the Alzheimer's animal model, age and sex, as well as the markers used to analyze the neurogenesis, the results indicated both a decrease, unchanged or even increased levels of neurogenesis both in animal models, and even in patients suffering from Alzheimer's disease in smaller number of studies. Previous results indicate the important role of members of the SOXB group of transcription factors in numerous cellular processes involved in neurogenesis during embryonic and adult developmental periods, such as the maintenance of multipotency, proliferation and differentiation of neural stem/precursor cells. In addition to SOXB transcription factors, certain neurotrophic factors, such as the brain derived neurotrophic factor (BDNF), affect the processes of proliferation and differentiation of neural stem/precursor cells. However, the exact role of these factors in the patogenesis of various neurodevelopmental and neurodegenerative disorders is not sufficiently clarified. Bearing in mind the above, the aim of this study was to determine the pattern of age-dependent changes in the expression of SOXB transcription factors within the adult neurogenesis process in male and female individuals and to examine the changes in the expression of SOXB transcription factors in the 5xFAD mouse model of Alzheimer's disease of both sexes and different ages..

Analysis of neurogenesis alterations in the subgranular zone of the hippocampus in a mouse model of Alzheimer's disease

Alchajmerova bolest je progresivno neurodegenerativno oboljenje i najčešći uzrok demencije kod starijih osoba, sa prevalencom dva puta većom u ženskoj populaciji. Jedna od struktura koje najranije bivaju zahvaćene patohistološkim promenama u AB je hipokampus, deo limbičkog sistema koji ima važnu ulogu u procesima učenja i formiranja memorije. Nova istraživanja potvrdila su da se i kod ljudi u subgranularnoj zoni hipokampusa aktivno odvija proces neurogeneze u adultnom periodu. Imajući u vidu činjenicu da novostvoreni neuroni imaju ulogu u procesima učenja i pamćenja, odnosno da utiču na oblikovanje kognicije i ponašanje individue, smatra se da se kognitivni deficit i gubitak pamćenja kod neurodegenerativnih oboljenja može delom pripisati poremećenoj neurogenezi na nivou subgranularne zone hipokampusa. Istraživanja procesa i dinamike adultne neurogeneze u hipokampusu životinja ili osoba obolelih od Alchajmerove bolesti su dala kontradiktorne rezultate. U zavisnosti od eksperimentalnih uslova, kao što su životinjski model Alchajmerove bolesti, starost i pol životinje, kao i markeri kojima se analiziraju ćelijski procesi, rezultati su ukazali kako na smanjenje, tako i na nepromenjen ili čak povećan obim neurogeneze kod animalnih modela i kod pacijenata obolelih od Alchajmerove bolesti. Dosadašnja istraživanja ukazuju na važnu ulogu članova SOXB grupe transkripcionih faktora u brojnim ćelijskim procesima uključenim u neurogenezu tokom embrionalnog i adultnog perioda razvoja, kao što su održavanje multipotentnosti, proliferacije i diferencijacije neuralnih matičnih/prekursornih ćelija. Pored SOXB transkripcionih faktora određeni neurotrofički faktori, kao što je neurotrofički faktor poreklom iz mozga (BDNF), utiču na procese proliferacije i diferencijacije neuralnih matičnih/prekursornih ćelija. Međutim, tačna uloga ovih faktora u nastanku različitih neurorazvojnih i neurodegenerativnih poremećaja nije dovoljno razjašnjena. Imajući u vidu navedeno, cilj ove studije bio je da se utvrdi obrazac uzrasno-zavisnih promena u ekspresiji SOXB transkripcionih faktora u okviru procesa adultne neurogeneze kod jedinki muškog i ženskog pola, kao i da se ispitaju promene u ekspresiji SOXB transkripcionih faktora kod 5xFAD mišjeg modela Alchajmerove bolesti oba pola i različite starosti...Alzheimer's disease is a progressive neurodegenerative disease and the most common cause of dementia in the elderly, with a prevalence of two times higher in the female population. One of the earliest affected structures by pathohistological changes in AB is the hippocampus, a part of the limbic system that plays an important role in the processes of learning and memory formation. New research has confirmed that even in humans the neurogenesis process actively occurs through the adult period in the subgranular zone of the hippocampus. Bearing in mind the fact that newly created neurons play a role in the processes of learning and memory, affecting the cognition and behavior of an individual, cognitive deficit and memory loss in neurodegenerative diseases can be partly attributed to altered neurogenesis at the level of the hippocampal subgranular zone. Analysis of the adult neurogenesis processes in the hippocampus of animals or persons suffering from Alzheimer's disease have resulted in contradictory data. Depending on experimental conditions, such as the Alzheimer's animal model, age and sex, as well as the markers used to analyze the neurogenesis, the results indicated both a decrease, unchanged or even increased levels of neurogenesis both in animal models, and even in patients suffering from Alzheimer's disease in smaller number of studies. Previous results indicate the important role of members of the SOXB group of transcription factors in numerous cellular processes involved in neurogenesis during embryonic and adult developmental periods, such as the maintenance of multipotency, proliferation and differentiation of neural stem/precursor cells. In addition to SOXB transcription factors, certain neurotrophic factors, such as the brain derived neurotrophic factor (BDNF), affect the processes of proliferation and differentiation of neural stem/precursor cells. However, the exact role of these factors in the patogenesis of various neurodevelopmental and neurodegenerative disorders is not sufficiently clarified. Bearing in mind the above, the aim of this study was to determine the pattern of age-dependent changes in the expression of SOXB transcription factors within the adult neurogenesis process in male and female individuals and to examine the changes in the expression of SOXB transcription factors in the 5xFAD mouse model of Alzheimer's disease of both sexes and different ages..

Structural features of arterial grafts important for surgical myocardial revascularization: Part II - Histology of the radial, inferior epigastric, and right gastroepiploic arteries

[Projekat Ministarstva nauke Republike Srbije, br. 175005, 175061, III41002, III45005 i 41022

Structural features of arterial grafts important for surgical myocardial revascularization: Part I - Histology of the internal thoracic artery

[Projekat Ministarstva nauke Republike Srbije, br. 175005, 175061, III41002, III45005 i 41022

Correlation of structural defects in the ascending aortic wall to ultrasound parameters: benefits for decision-making process in aortic valve surgery

Abstract Background Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered. Methods Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA. Results Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p  3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. Conclusions Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR

Myocardial Na+ K+-ATPase and SERCA: Clinical and Pathological Significance From a Cytological Perspective

Structure and functions of Na+/K+-ATPase and SERCA are described with details on their subunits, isoforms, and intracellular localization. Main regulatory mechanisms are summarized. Molecular mechanisms of cell death and heart failure are explained with the analysis of the role of Na+/K+-ATPase and SERCA in these processes. Facts are considered from a cytological, pathological, and clinical perspective with an accent to new therapeutic strategies. The aim of this contribution is an overview of functional results in a structural context.Part of the Advances in Biochemistry in Health and Disease book series (ABHD,volume 15)