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The effect of a restricted feeding regimen of different duration on behavior and the mTOR signaling pathway in the cortex and hippocampus of aging male and female Wistar rats
No full textStarenje je složen biološki proces praćen postepenim gubitkom fizoloških funkcija i promenama u strukturi i funkciji svih sistema, pa i nervnog. Kao jedna od najefikasnijih intervencija u produženju životnog veka i odlaganju starosno zavisnih promena se pokazala dijetalna restrikcija (DR), definisana kao smanjenje kalorijskog unosa bez pothranjenosti. Međutim, o uticaju koji ima starost organizma i dužina trajanja DR na korisne efekte po kojima je DR poznata, se malo zna.
U ovoj studiji ispitan je uticaj 40% DR različitog trajanja i početka na promene telesne mase, preživljavanje, krhkost, ponašanje, ekspresiju dopaminskih receptora i mTOR signalizaciju kod mužjaka i ženki Wistar pacova. Kod 18-mesečnih ženki, DR je smanjila smrtnost, poboljšala memoriju i smanjila anksiozno ponašanje, bez obzira na to da li je započeta u ranom ili kasnom periodu života, dok je kod starih ženki efekat zavisio od trenutka otpočinjanja DR. Kod mužjaka, DR je povećala preživljavanje i smanjila krhkost, ali nije poboljšala memoriju, dok je anksioznost bila povećana u svim grupama. Ekspresija proteina mTOR signalnog puta se menjala u zavisnosti od pola, starosti organizma i dužune trajanja DR. Rezultati ističu ključnu ulogu pola i vremena otpočinjanja DR. Iako rezultati potvrđuju da je DR moćna strategija za zdravo starenje negativni efekti kasno započete DR naglašavaju važnost definisanja optimalnog vremenskog okvira za uvođenje DR, ukazujući na potrebu za personalizovanim pristupom u u intervencijama za odlaganje starosnih promena.Aging is a complex biological process characterized by a gradual loss of physiological functions accompanied with changes in the structure and function of all systems, including the nervous system. Dietary restriction (DR), defined as a reduction in caloric intake without malnutrition, has proven to be one of the most effective interventions for extending lifespan and delaying age-related changes. However, data are lacking on how the onset and duration of DR, as well as sex, influence its beneficial effects.
This study examined the effects of 40% DR of various duration and onset on body weight, survival, frailty, behavior, dopamine receptor expression, and mTOR signaling in male and female Wistar rats. In 18-month-old females, DR reduced mortality, improved memory, and decreased anxiety-related behavior, regardless of whether it was initiated early or late in life, while the effect in older females depended on the timing of when DR was initiated. In males, DR increased survival and reduced frailty, but did not improve memory, whereas anxiety was heightened in all groups. The expression of proteins in the mTOR signaling pathway varied depending on sex, age, and the duration of DR.
The results highlight the critical roles of sex and the timing of DR initiation. Although the findings confirm that DR is a powerful strategy for healthy aging, the negative effects of late-started DR emphasize the importance of defining an optimal timeframe for implementing DR, indicating the need for a personalized approach in interventions aimed at delaying age-related changes
The influence of microenvironment on the gene expression of Tnf-α, Il-1β and Il-6 in the A53T mouse model of Parkinson's disease
No full textThe differences in social microenvironment (i.e., whether animals are housed in mixed or
single genotype environments) could influence the behavioral and molecular outcomes in
preclinical research of neurodegenerative diseases. However, the potentially confounding effects
of social microenvironment in studies using transgenic animals have not been sufficiently
investigated. In this study we explored the influence of microenvironment on mRNA expression
of proinflammatory cytokines (TNFα, IL-1β and IL6) which are consistently reported to be
relevant to PD in clinical and preclinical settings. The Hualpha-Syn(A53T) transgenic mouse line
G2-3 (JAX006823 strain) as a model of Parkinson's disease (PD) was used and the brain regions
of interest were the medial prefrontal cortex (mPFC) and the hippocampus (HPP).
Five groups of male mice were formed at post-natal day (PND) 30: transgenic hemizygous
A53T carriers (A53T+) kept in mixed-genotype housing (MGH) and single genotype housing
(SGH); their non-transgenic littermates (A53T-) kept in MGH and SGH; as well as, C57BL/6J
animals (used in backcrossing of the colony) which served as controls. On PND 190 (the pre-motor
stage) the mPFC and HPP of all animals were extracted for RT PCR analysis. mRNA expression
of TNFα, IL-1β and IL6 was assessed.
The microenvironment slightly influenced IL-1β mRNA expression in the HPP of A53T+
mice. Specifically, there was a trend (p=0.052) of differences in IL-1β expression between A53T+
mice in SGH and those in MGH, with higher fold-change percentage observed in MGH. The
difference in expression of Tnf-α in the mPFC between A53T+ mice in SGH and C57BL/6J
controls was statistically significant, while the difference in Tnf-α expression between A53T+
mice in MGH and C57BL/6J controls was marginally significant (p=0.052).
Our findings emphasize the need to control housing conditions in studies using transgenic
animals considering that certain biochemical characteristics of the model were sensitive to
variations in microenvironments. Future studies should explore in depth how other biochemical
indicators and neuro-behavioral characteristics of the model can potentially be affected by the
social microenvironment.(presentation) Belgrade Neuroscience Next Hub 2025 with international participation; 2025 Feb 27; Belgrade, Serbia. Belgrade: University of Belgrade, Faculty of Medicine; 2025
The Effects of Alfaxalone on Neuroinflammation and Neurodegeneration in the Cortex of Female APP knock-in mice
No full textAlzheimer’s disease (AD) is a progressive age-associated neurodegenerative disorder and the leading cause of dementia among the elderly. A naturally occurring neurosteroid, allopregnanolone, was shown to have neuroprotective effects and decrease amyloid-beta deposition and consequent neuroinflammation and neurodegeneration in animal models AD. Its synthetic neurosteroid analogue Alfaxalone (ALX) have improved bioavailability and was demonstrated not to develop tolerance with extended use. In the present study, the effects of ALX treatment on pathological markers were examined in the APP NL-G-F knock-in (KI) mouse model of AD. The 9-month-old female KI mice and their non-KI littermates (wild-type, WT) were treated with two doses of ALX (10 and 40 mg/kg; s.c, 1/w) for four weeks. After the end of the treatment, the effects on key histopathological markers, amyloid plaques, and consequent gliosis were examined in the cerebral cortex, brain regions important for learning and memory. Histochemical dye Thioflavin S (ThS) was used for amyloid β plaque visualization, while ionized calcium-binding adapter molecule 1 (Iba-1) was used as a marker for labeling microglial cells by immunohistochemistry. Morphological analysis of plaque number and average size was accompanied by the full characterization of microgliosis performed by quantitative analysis of the relative intensity of fluorescence signal for Iba-1 expression. Our findings demonstrate that both doses had neuroprotective effects and reduce amyloidosis in female KI mice. Future studies are warranted to more comprehensively determine the effects of ALX on AD-associated cognitive and behavioral deficits.Marjanović A, Milovanović N, editors. Book of abstracts: Belgrade Neuroscience Next Hub 2025 with international participation; 2025 Feb 27; Belgrade, Serbia. Belgrade: University of Belgrade, Faculty of Medicine; 2025. p. 31-2
Plum cultivars grown in Norway
No full textThis report presents results of plum cultivars and selections studies, performed during 2018-2021 at NIBIO Ullensvang, Njøs Fruit and Berry Centre and Norwegian University of Life Sciences (NMBU) in the frame of FRUIT-N-QUALITY (Evaluation of traditional Norwegian apple, plum and raspberry cultivars) project.
The aim of this study was to evaluate Norwegian heritage plum cultivars from pomological, agronomical, and biochemical point of view, identify the most important quality parameters, and select cultivars with desirable traits for modern markets and breeding purposes.
In total 64 heritage plum cultivars were evaluated. Along with some commercial cultivars and new selections, heritage cultivars Edwards, Prosser 84, Yakima, Belle de Louvain and Thames Cross have all very big fruits (71 – 90 g).
Cultivars Experimentalfältets Sviske, Reine Claude Grøn and Italiensk Sviske accumulated the highest soluble solid content.
Cultivars Sinikka, Grand Duke, Italiensk Sviske, Sviske frå Tveit and Vinterplomme had the most acid fruits.
Cultivars Bleue de Belgique, Reine Claude Grøn, Vinterplomme, and Mount Royal accumulated the highest fruit phenol content.
Cultivars Jefferson, Mallard and Mount Royal had the most aromatic fruits.
13 cultivars and selections received very high overall sensor evaluation (taste, attractiveness, aroma) score, among them heritage cultivars Helgøyplomme, Reine Claude d'Althanns and Mallard.
In addition, the chemical contents of the fruits and the kernels are listed for 60 cultivars
Soil mosaic: A multi-modelling approach to understand the complex interactions that determine the spatial heterogeneity of soil health − An example from Serbia
No full textIn this study, an integrated and explainable modelling framework is applied to assess soil health and its spatial heterogeneity in Eastern Serbia. The approach combines Network Analysis (NA), Self-Organizing Maps (SOM) and the Geodetector Model (GDM) to identify key soil indicators, reveal spatial patterns and quantify the influence of environmental factors. The main objectives were: (i) to develop a scalable and transferable methodology to assess soil health, (ii) to identify the most influential natural and anthropogenic factors and (iii) to create a Soil Health Disturbance Index (SHDI) to visualise the impact at ecosystem level. A total of 2,555 soil samples were analysed using fourteen key indicators, while nine environmental variables were considered as potential influencing factors. The network analysis identified pH, cadmium (Cd) and potassium (K) as the most central elements within the soil system. SOM clustering revealed five different spatial patterns associated with dominant soil processes, while GDM results emphasised soil type (Q = 0.26) and parent material (Q = 0.24) as the strongest individual influencing factors. In particular, interactive effects such as soil type ∩ soil erosion (Q = 0.47) indicated a significant nonlinear amplification of soil health disturbances. The SHDI results showed that 26.9 % of the region is categorised as highly disturbed, mainly in urban and industrial areas. Overall, the proposed framework enhances the diagnostic capacity for soil health assessment and offers practical support for sustainable soil management and evidence-based spatial planning
Overcoming the challenges in cryptic species recognition – the case of the strictly protected European lesser blind mole rat
No full textWildlife monitoring can be a challenge when speciation is not always followed by morphological changes, i.e. cryptic species, the recognition of which is the first necessary step. Here, we present the case of the subterranean rodent European lesser blind mole rat (BMR) Nannospalax leucodon supersp. which comprises more than 20 chromosomal forms, five of which occur in Serbia and are strictly protected by law. Despite reproductive isolation and phylogenetic distance confirmed among these five chromosomal forms/cryptic species, they are not officially designated as species due to morphological convergence. From a conservation perspective, it is essential to monitor their populations and describe their distribution areas. Our approach combines karyotyping with molecular genetic species identification and sex determination. Since all known BMR's karyotyping protocols required animal sacrifices, we developed the only possible non-lethal sampling method using finger snips followed by the safe return of animals to their original underground systems. Additionally, standard procedures for mammalian fibroblast growth were not applicable due to the specific cell culture characteristics related to BMR’s resistance to cancer. The composition of the complete medium followed the standard fibroblast protocol, with minor modifications. However, the karyotyping protocol (colchicine, ethidium bromide and the type of hypotonic solution) was significantly changed compared to other rodent species. For rapid and reliable species identification, we developed the Inter Simple Sequence Repeat ˗ PCR profiling technique. Of 11 different ISSR primers tested for the presence of species-specific DNA fragments, three primers provided informative DNA profiles that ensured reliable and unambiguous recognition of analysed cryptic species. Sex of each individual was determined through PCR-based sry determination presented as sry marker presence/absence. Our results demonstrate the efficacy of these methods and provide a reproducible model for monitoring other cryptic species. This research underscores the importance of non-lethal genetic monitoring for biodiversity conservation.Mitsainas GP, Borowski Z, Georgiakakis P, Henttonen H, Lymberakis P, Schley L, Youlatos D, editors. Book of abstracts: IX European Congress of Mammalogy (ECM9); 2025 Mar 31 - Apr 4; Patras, Greece. European Mammal Foundation; 2025. p. 297
Soil eDNA-based droplet digital PCR assay as a new monitoring tool for terrestrial mammals
No full textThis study demonstrates the effectiveness of droplet digital PCR (ddPCR) for identifying vertebrate taxa from soil-derived environmental DNA (eDNA) – a methodological combination not previously documented in literature. The protocol is optimized for detecting cryptic species of the lesser blind mole rat (BMR). A total of 38 soil samples were collected from five cryptic BMR species across 12 localities in Serbia. Species-specific primer/probe sets were designed based on the cytochrome b (cytb) gene. After optimization of ddPCR assays and verification of primer/probe specificity, all samples were amplified in triplicates and the results’ significance was tested using the RStudioV4.3.3 Environment. The total number of positive findings was detected in 33 out of 38 samples (86.84 %), highlighting the strength of ddPCR in detecting and quantifying rare and degraded target DNA from soil samples. Concentration values varied from 0.073 to 236 copies/µL. The primer/probe sets were highly specific and the only difficulty emerged in distinguishing between two phylogenetically closest cryptic species, but with a discrepancy in fluorescence amplitudes in specific (target) and non-specific (non-target) cryptic species. We have confirmed that soil eDNA-based ddPCR species identification is a fast and highly sensitive non-invasive monitoring method. It allows quick and easy sampling of many locations across wide areas, providing essential data for conservation management. This protocol offers a valuable framework for conservation strategies targeting cryptic species, while also serving as a foundation for adaptation and broader implementation across other terrestrial vertebrates of concern – particularly those that are strictly protected or classified as endangered
In vitro evaluation of indole-3-carboxyaldehyde as a potential modulator of experimental MASLD
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent
chronic liver disease in Western countries and continues to increase worldwide. Lifestyle
interventions remain the cornerstone of treatment, but are often insufficient, particularly in
patients with progressive forms of the disease, for which there are currently no approved
pharmacological treatments in Europe. This underscores the urgent need for novel therapeutic
options, and microbiota-derived metabolites are emerging as promising candidates.
Using untargeted metabolomics approach, plasma samples from 122 participants (MASLD
patients and BMI- and age- matched controls) were analyzed using UHPLC-QTOF-MS.
Among the 1315 polar metabolites detected, indole-3-carboxyaldehyde (I-3-A) was identified
as significantly less abundant in MASLD patients, based on limma univariate analysis. Given
its microbial origin and known activity as an agonist of the aryl hydrocarbon receptor (AhR),
this metabolite was selected for further functional studies.
We are assessing the effects of I-3-A in palmitic acid-treated hepatic cells that mimic fatty liver
conditions. Two hepatocyte-derived cell lines were used: human HepaRG and murine AML12,
in order to ensure translational relevance to human physiology, while also providing
information for future in vivo studies. Key endpoints are including the expression of AhR target
genes, pro-inflammatory cytokines, and fibrotic markers, to better understand the potential of
I-3-A as a modulator of MASLD pathophysiology. Our results are expected to demonstrate
protective effect of I-3-A on liver inflammation and fibrosis and lay a basis for development of
novel therapeutics.Book of Abstracts: XVI iMed.ULisboa Postgraduate Students Meeting; 2025 Jul 1-2; Lisbon, Portugal. iMED.ULisboa Postgraduate Students Commission; 2025. p. 61
Postnatal overfeeding induces gut microbiota disturbances and impairs GPR43/FIAF/LPL pathway in the rat model of PCOS
No full textWomen with polycystic ovary syndrome (PCOS) has high incidence of metabolic dysfunction-associated steatotic liver
disease (MASLD). The development of PCOS-associated MASLD is accelerated by prepubertal obesity, therefore, we
analyzed the impact of postnatal overfeeding-induced obesity on the gut microbiota and hepatic lipid metabolism in the
PCOS rat model. Wistar rats were divided into 4 groups, where treatment with 5α-dihydrotestosterone (5α-DHT) stimulated hyperandrogenemia (DHT groups), whereas litter size reduction induced early postnatal overfeeding and obesity (SL
groups). The fecal microbiota composition and diversity was analyzed by 16S rRNA sequencing. The bacterial metabolites
level was measured by mass spectrometry. Hematoxylin–eosin staining, Western blots, and qRT-PCR were used to analyze
hepatic lipid metabolism. Our results show that postnatal overfeeding shifted the microbiota composition towards obesityassociated genera, while hyperandrogenemia led to reduced β-diversity and increased abundance of androgen-regulated
genera. Interaction of treatments reduced α- and β-diversity and decreased the abundance of beneficial butyrate-producing
genera Roseburia, Oscillospira, and Ruminococcus and butyric acid plasma level. Shift in microbiota composition and activity was accompanied by decreased expression of G-protein coupled receptor (GPR) 43, fasting-induced adipocyte factor
(FIAF) and increased expression of lipoprotein lipase (LPL). In accordance with altered GPR43 and FIAF/LPL pathway,
increased expression of lipogenic transcription factors was observed in SL-DHT animals, but this did not result in hepatic
lipid deposition. Our results demonstrated that postnatal overfeeding contributes to decreased richness and changes in gut
microbiota composition in the PCOS animal model that is associated with impaired hepatic lipid metabolism, which may
accelerate development of MASLD
Temperature as a Factor Shaping Dissolved Oxygen in the Danube River
No full textThe health of terrestrial waters is of utmost importance for the sustenance of aquatic ecosystems, and dissolved oxygen (DO) represents one of the key indicators used to evaluate water health. In this study, the objective was to predict DO levels in the Danube river, using data on flow velocity and temperature, and to investigate intricate relationships among these variables. Firstly, a Random Forest regression algorithm was deployed to predict DO levels using flow velocity and temperature as predictors, and SHapley Additive exPlanations (SHAP) values were calculated. Then, an autocorrelation function was integrated into the Random Forest regression algorithm, incorporating DO data from previous time steps. Autocorrelation and partial autocorrelation functions, together with partial and cross-correlation analyses were also performed. Altogether, DO levels predicted, using flow velocity and temperature, resulted in model with R2 equal to 0.88 (MSE = 0.59; RMSE = 0.77), and SHAP values highlighted that temperature exerted a more pronounced influence on DO levels than flow velocity. When DO data from previous time steps were used, this enhanced model achieved an R2 equal to 0.97 (MSE = 0.11; RMSE = 0.33) and DO from preceding time steps had the most substantial influence on the predictive accuracy of this model. Autocorrelation and partial autocorrelation function plots for DO, underlined its strong correlation with adjacent time steps values. Partial and cross-correlation analyses revealed that temperature exhibited a strong negative correlation with DO. In conclusion, this research provides valuable insights into the dynamics governing terrestrial water health, emphasizing the indispensable role of temperature in modulating DO levels.Filipović N, editor. Applied Artificial Intelligence 4: Medicine, Biology, Chemistry, Financial, Games, Engineering: The Third Serbian International Conference on Applied Artificial Intelligence (SICAAI); 2024 May 23-24; Kragujevac, Serbia. Cham: Springer; 2025. p. 135-41. (Lecture Notes in Networks and Systems (LNNS); Vol. 1446)