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The Impact Of Dietary Restriction On Memory Performance And Anxiety Of Adolescent Female Wistar Rats
No full textAdolescence is a critical phase for brain development marked by substantial changes in both brain structure and function. This period is often linked to the onset of various neuropsychiatric disorders due to these changes leading to observable behavioral issues. Additionally, adolescence is influenced by numerous external factors, with dietary restriction (DR) being one of the most researched. DR has been shown to improve cognitive abilities, memory, and learning, although its impact can differ based on several factors, including the age at which it is implemented.
This study investigated how a 30% DR (70% of ad libitum daily intake) during adolescence affects spatial working memory and anxiety-like behavior in adolescent female Wistar rats. The dietary restriction was implemented at three different stages: DR1 (28th to 35th postnatal day), DR2 (35th to 42nd postnatal day), and DR3 (28th to 42nd postnatal day). Behavioral assessments were conducted on postnatal days 52 and 53, corresponding to late adolescence. The Y maze test was used to evaluate spatial working memory, while the light-dark box test was used to assess anxiety-like behavior.
The results indicated that the DR1 experimental group demonstrated slightly better memory performance compared to the control group of the same age, while the DR2 and DR3 groups showed poorer memory performance. In the light-dark box test, the DR1 group made more entries into the light area and spent more time there. On the other hand, both DR2 and DR3 groups entered the light zone less frequently and spent less time there.
In conclusion, the effects of DR differ based on the adolescent stage at which it is applied. The use of DR1 has enhanced memory performance and lowered anxiety about open and light spaces in late adolescent females. Conversely, treatments DR2 and DR3 have negatively impacted memory performance of late adolescent females and heightened their anxiety in comparable settings.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. 34
ADHD-like behaviors in adolescent mice prenatally exposed to levetiracetam: No safe gestational dose across sexes
No full textAdministering medication during pregnancy is always a challenging task. Levetiracetam (LEV), a second-generation antiepileptic drug, has been recognized as relatively safe based on studies assessing neurodevelopmental outcomes of children exposed to it in utero, despite some animal research reporting skeletal abnormalities. The potential link between intrauterine exposure to subtherapeutic or therapeutic doses of LEV and behavioral abnormalities in adolescent offspring has not yet been examined. The present study aimed to investigate the effects of maternal exposure to LEV at doses of 158, 211, and 316 mg/kg/day during mating and throughout gestation on behavioral abnormalities in offspring during the periadolescent period, using a mouse model. The selected doses correspond to clinical human LEV doses of 750, 1000, and 1500 mg/day. To assess the quantitative and qualitative parameters of behavioral response, the elevated plus-maze test (EPMT) on postnatal day (PND) 37 and the open field test (OFT) on PND45 were used. Experimental animals prenatally exposed to subtherapeutic or therapeutic doses of LEV exhibited complex and qualitatively different behaviors during the periadolescent period. The study's findings suggest that different doses of LEV administered throughout gestation may alter brain maturation patterns in offspring, leading to behavioral changes during periadolescence. In both the EPMT and OFT, offspring of mothers exposed to different doses of LEV displayed hyperactivity and stereotypy, observed in both females and males. The results revealed a non-linear, dose-dependent effect on behavior. This suggests that the model may be applicable as an animal model for attention-deficit/hyperactivity disorder (ADHD)
Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance
No full textAnticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of chemotherapy and targeted therapies. Conventional two-dimensional (2D) cell cultures cannot replicate the complexity of the in vivo tumor microenvironment (TME), limiting their utility for drug resistance research. Therefore, three-dimensional (3D) tumor models have proven to be a promising alternative for investigating chemoresistance mechanisms. In this review, various cancer 3D models, including spheroids, organoids, scaffold-based models, and bioprinted models, are comprehensively evaluated with a focus on their application in drug resistance studies. We discuss the materials, properties, and advantages of each model, highlighting their ability to better mimic the TME and represent complex mechanisms of drug resistance such as epithelial-mesenchymal transition (EMT), drug efflux, and tumor-stroma interactions. Furthermore, we investigate the limitations of these models, including scalability, reproducibility and technical challenges, as well as their potential therapeutic impact on personalized medicine. Through a thorough comparison of model performance, we provide insights into the strengths and weaknesses of each approach and offer guidance for model selection based on specific research needs
Metabolomic and transcriptomic responses to waterlogging stress and hydrogen peroxide elicitation: impact on the production of iridoids and phenolics in leaves of two Nepeta species
No full textNepeta species, known for their diverse bioactive metabolites, particularly iridoid and phenolic compounds, have recently attracted growing interest due to their biotechnological potential and ability to cope with various environmental stresses. This study was aimed at leveraging the specialized metabolism of chemically distinct Nepeta nuda and N. grandiflora by applying waterlogging (W), hydrogen peroxide (H₂O₂), or a combination of both stresses. These treatments are anticipated to trigger H2O2-responsive signaling pathways that regulate the biosynthesis of terpenes and phenolics. Following the exposure to W and/or H2O2 treatments, species-specific patterns of changes in leaf metabolomes and transcriptomes were recorded. Prominent increase of nepetalactone (NL) content in N. nuda (up to 12-fold) and slight increase of 1,5,9-epi-deoxyloganic acid (1,5,9-eDLA) in leaves of NL-lacking N. grandiflora (up to 1.5 fold) were conditioned by upregulation of iridoid biosynthesis-related genes, especially those encoding for NAD-dependent nepetalactol-related short-chain-dehydrogenase/reductases (NEPSs) responsible for setting the NL stereochemistry and for regulating metabolic flux through the iridoid pathway. NL content is apparently more susceptible to oxidative stress-induced alterations than that of iridoid glycosides. Although H2O2 and W/H2O2 treatments significantly stimulated the accumulation of rosmarinic acid, especially in leaves of N. nuda, the expression levels of the majority of the corresponding biosynthetic genes were only slightly upregulated. N. nuda leaves also displayed higher antioxidant potential than those of N. grandiflora, suggesting either superior capacity of the former species to mitigate oxidative stress, or higher tolerance of N. grandiflora. Although overlapping response mechanisms to the two applied stresses were expected to exert an additive burden on Nepeta specialized metabolism, this was not observed as the H2O2 and W/H2O2 treatments proved equally effective. While the mechanistic basis of the targeted stress elicitation requires further investigation, the present study underscores its biotechnological potential for upscaling the production of iridoids and phenolics in Nepeta species
Exploring Manganese Accumulation in Euphorbia: Insights from Herbarium Specimens Using Portable XRF Spectroscopy
No full textHerbarium collections play a crucial role in botanical research and serve as invaluable repositories of plant
diversity. Non-invasive scanning of the metal and metalloid content of herbarium specimens provides
important insights into historical and geographical patterns of element accumulation and contributes to
ecological, physiological and phylogenetic studies as well as to the discovery of new potential
hyperaccumulators of metal(loid)s.
Five taxa of the genus Euphorbia from south-eastern Europe (Euphorbia spinosa subsp. glabriflora and
subsp. spinosa, E. montenegrina, E. serpentini, and E. verrucosa) were analysed using hand-held X-ray
fluorescence spectroscopy (XRF). The samples were analysed in the collections of the Herbarium of the
University of Belgrade and the Herbarium of the University of Innsbruck. The analysed plant samples
originate from eleven European countries, mainly from the Balkan Peninsula and the Mediterranean region.
Manganese concentrations in the analysed samples ranged from 100 to 4900 mg kg-1, with median
concentration of 756 mg kg-1. The highest concentrations of Mn (>4000 mg kg-1) were found in E. spinosa
subsp. glabriflora from an ultramafic site on Mt. Tara in W Serbia and from a limestone site in Nemërçkë
in Albania. In addition, manganese concentrations of over 3000 mg kg-1 were found in E. montenegrina
from Bosnia and Herzegovina, while a concentration of 2960 mg kg-1 was measured in E. spinosa from
Zadar, Croatia. Although the measured manganese concentrations in Euphorbia samples do not exceed the
nominal hyperaccumulation threshold of 10,000 mg kg-1, the observed values indicate an unusually high
accumulation potential in certain taxa, especially E. spinosa subsp. glabriflora that predominately occurs
on ultramafics. These results warrant further investigation, including controlled dose trials, to explore the
physiological and ecological mechanisms underlying manganese accumulation in this genus.11th International Conference on Serpentine Ecology: ICSE2025; 2025 Jun 13-17; Kyoto, Japan. Kyoto Institute, Library and Archives; 2025. p. 138
Apoptosis-induced compensatory proliferation: optimization of colorectal cancer mouse model and establishment of mouse-derived organoids
No full textIntroduction. Recent data suggest a paradoxical link between the dyingcells in tumor tissue and accelerated tumor growth.Dying tumor cells trigger a "regeneration" process"through a signaling pathway known as "Phoenix rising".To delineate the process of therapy-induced repopulation
in advanced colorectal cancer, we developed a mousemodel that mimics communication between dying andlive cells in a tumor microenvironment (TME).Following the 3R principle in animal experiments, we established mouse-derived organoids from these tumors and used transcriptional analysis to confirm whether this complex 3D model could mirror TME and be used in comprehensive drug screening in the future. Material and method. The appropriate mouse model representing apoptosisinduced compensatory proliferation was developed by subcutaneous inoculation of the mixture of live and dead MC38 cells into C57BL/6 mice. The dead cells were collected after in vitro treatment with 5-fluorouracil. During the optimization, the number of live cells and the ratio between live and dead cells in the mixture were varied and finally determined. Additional groups representing controls received the same number of only live or only dead MC38 cells. Also, the group receiving
the optimal number of MC38 cells to form tumors in the classic animal model was used for comparison. After tumor isolation, one part of each tumor was frozen, and the other part was digested and used to establish mousederived organoids. Both tumors and organoids derived from the compensatory proliferation model and classic model were further analysed by RNA sequencing. Result and discussion. The group that received only live MC38 cells had a low incidence rate and slow tumor growth rate. However, when the same number of live cells is injected with dead cells in a 1:50 ratio, the tumors' earlier onset, fast growth, and 100% incidence rate revealed that this type of inoculation dramatically enhanced tumor aggressiveness. The transcriptional analysis of isolated tumors and their
matching organoids from two different models of disease showed 80% of gene expression homology, indicating that organoids represent a valid model system for drug screening. Conclusion. The suitable mouse model reflecting compensatory proliferation in colorectal cancer was established and compared to the typical form of the disease, showing important features that can be used as targets to prevent tumor repopulation and thus amplify the effect of chemotherapy.EACR 2025 Congress: Innovative Cancer Science; 2025 Jun 16-19; Lisbon, Portugal. John Wiley and Sons; 2025. p. 749. (Molecular Oncology; Vol. 19; Suppl. 1)
Trening škola eksperimentalne evolucije 2024 - Izveštaj
No full textNajvažniji cilj trening škole eksperimentalne evolucije bio je da se studentima pruži prilika da se upoznaju sa savremenim pristupima u evoluciono-biološkim istraživanjima i da ovladaju veštinama čitanja naučnih radova i pisanja predloga istraživanja koje će im pomoći u budućem radu. Trening školu eksperimentalne evolucije organizovali su saradnici na ELEVATE projektu finansiranog od strane Fonda za nauku Republike Srbije u okviru programa IDEJE. Trening škola eksperimentalne evolucije studentima je predstavila raznovrsnost i primenu eksperimentalne evolucije u istraživačkom radu. Polaznici trening škole upoznali su se sa: 1) teorijskim osnovama ovog metodološkog pristupa u savremenim biološkim istraživanjima; 2) istraživanjima na pasuljevom žišku i rezultatima primene eksperimentalne evolucije na ovom model organizmu; 3) praktičnim radom dizajniranja eksperimenata primenom eksperimentalne evolucije
Goat’s Milk Powder Enriched with Red (Lycium barbarum L.) and Black (Lycium ruthenicum Murray) Goji Berry Extracts: Chemical Characterization, Antioxidant Properties, and Prebiotic Activity
No full textThe current trend in food innovations includes developing products containing plant ingredients or extracts rich in bioactive compounds. This study aimed to prepare and characterize skimmed thermally treated goat’s milk powders enriched with lyophilized fruit extracts of Lycium ruthenicum Murray (GMLR) and Lycium barbarum L. (GMLB). Proximate analysis, ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), Fourier transform infrared spectroscopy using attenuated total reflection (FTIR-ATR), and electrophoretic analysis were assessed. Total phenolic content (TPC), total protein content, and antioxidant properties of enriched goat milk powders were determined spectrophotometrically, and prebiotic potential was evaluated by the broth microdilution method. A total of 25 phenolic compounds and 18 phenylamides were detected in the enriched goat milk powders. Electrophoretic analysis showed the absence of proteolysis in the prepared powders. The GMLR showed the highest TPC and displayed a ferric ion-reducing power, probably contributed by anthocyanins and some phenylamides. GMLR and GMLB had higher ABTS radical scavenging activity but lower ferrous ion-chelating capacity than control goat′s milk powder. GMLB and GMLR in a dose-dependent manner (0.3–5 mg/mL) showed a growth-promoting effect on probiotic strains. In summary, prepared goji/goat milk powders, primarily GMLR, might be used as prebiotic supplements or functional food additives
The bioherbicidal potential of hemlock water extracts
No full textStudying plant species rich in bioactive compounds, including allelochemicals,
could lead to the development of biodegradable and environmentally safe herbicides. In this
study, a water extract of hemlock (Conium maculatum L.), known to be rich in alkaloids, was
used to investigate its effects on the germination of Amaranthus retroflexus L., Ambrosia
artemisiifolia L., Stellaria media (L.) Vill., and Lactuca sativa L., providing valuable insights
into its phytotoxic properties. Among the C. maculatum water extracts (CmWEs) tested, that
of dry leaves showed the strongest inhibitory effect on the germination of all species analyzed.
The CmWE of dry leaves (50%) completely inhibited seed germination of all species tested.
The CmWE of dry stems (50%) reduced seed germination in S. media, A. retroflexus, and A.
artemisiifolia by 20% to 89%, whereas the germination of L. sativa was less affected (9%). In
addition, a CmWE of dry stems (5%) selectively inhibited ragweed germination (45%), while
the germination of Lactuca sativa was not significantly affected. The CmWE of dry leaves
(20%) inhibited early root and shoot growth of S. media more effectively than suppressing seed
germination. Moreover, the dry leaves and inflorescences of C. maculatum demonstrate strong
allelopathic properties even after two years of storage, highlighting the long-term potential of
C. maculatum as a source of natural herbicides
Implications of mitonuclear interactions for the Trojan Female Technique in pest biocontrol: A case study on the seed beetle Acanthoscelides obtectus
No full textThe seed beetle (Acanthoscelides obtectus) is a pest of common beans and other legumes that causes considerable losses of stored products. Its populations are universally regulated with insecticides, but novel, safer and more efficient methods of control are needed. One such method is the Trojan Female Technique (TFT) which is based on the existence of male harming/female benign mitochondrial haplotypes. The introduction of females carrying haplotypes with male-specific negative effect into the target population can lead to its self-perpetuating suppression over generations. Due to the coevolution of mitochondrial and nuclear genomes, it is possible for nuclear variants that compensate for the negative effects of male harming mitochondrial haplotypes to evolve. Therefore, one of the requirements for the applicability of TFT is that candidate mitochondrial haplotypes confer their negative effects on males in diverse nuclear backgrounds. In this study, we used the previously described mitochondrial haplotype, MG3b, which reduces male-only fertility, and placed it in a range of nuclear backgrounds from three different natural populations. The goal was to test whether its effects on male and female fertility are dependent on interactions with different nuclei. Our results showed that MG3b consistently decreases male fertility independently of the nuclear environments, while having no negative effect on females. Additionally, we found no statistically significant effect of mitonuclear interactions, suggesting that there is no standing variation of compensatory mutations in nuclear backgrounds. These results indicate that the MG3b haplotype could be used in the TFT in different natural seed beetle populations