Search Results (203)

Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

This study identifies and classifies resistance gene analogues (RGAs) in the genomes of Brassica nigra, Sinapis arvensis and Sinapis alba using the RGAugury pipeline. RGAs were categorised into four main classes: receptor-like kinases (RLKs), receptor-like proteins (RLPs), nucleotide-binding leucine-rich repeat (NLR) proteins and transmembrane-coiled-coil (TM-CC) genes. A total of 4499 candidate RGAs were detected, with species-specific proportions. RLKs were the most abundant across all genomes, followed by TM-CCs and RLPs. The sub-classification of RLKs and RLPs identified LRR-RLKs, LRR-RLPs, LysM-RLKs, and LysM-RLPs. Atypical NLRs were more frequent than typical ones in all species. Atypical NLRs were more frequent than typical ones in all species. We explored the relationship between chromosome size and RGA count using regression analysis. In B. nigra and S. arvensis, larger chromosomes generally harboured more RGAs, while S. alba displayed the opposite trend. Exceptions were observed in all species, where some larger chromosomes contained fewer RGAs in B. nigra and S. arvensis, or more RGAs in S. alba. The distribution and density of RGAs across chromosomes were examined. RGA distribution was skewed towards chromosomal ends, with patterns differing across RGA types. Sequence hierarchical pairwise similarity analysis revealed distinct gene clusters, suggesting evolutionary relationships. The study also identified homologous genes among RGAs and non-RGAs in each species, providing insights into disease resistance mechanisms. Finally, RLKs and RLPs were co-localised with reported disease resistance loci in Brassica, indicating significant associations. Phylogenetic analysis of cloned RGAs and QTL-mapped RLKs and RLPs identified distinct clusters, enhancing our understanding of their evolutionary trajectories. These findings provide a comprehensive view of RGA diversity and genomics in these Brassicaceae species, providing valuable insights for future research in plant disease resistance and crop improvement. Full article

Previous studies have suggested that T14, a 14-amino-acid peptide derived from acetylcholinesterase (AChE), functions as an activity-dependent signalling molecule with key roles in brain development, and its dysregulation has been linked to neurodegeneration in Alzheimer’s disease. In this study, we examined the distribution of T14 under normal developmental conditions in the mouse forebrain, motor cortex (M1), striatum (STR), and substantia nigra (SN). T14 immunoreactivity declined from E16 to E17 and further decreased by P0, then peaked at P7 during early postnatal development before declining again by adulthood at P70. Lower T14 immunoreactivity in samples processed without Triton indicated that T14 is primarily localised intracellularly. To explore the relationship between T14 expression and neuronal activity, we used mouse models with chronic silencing (Rbp4Cre-Snap25), acute silencing (Rbp4Cre-hM4Di), and acute activation (Rbp4Cre-hM3D1). Chronic silencing altered the location and size of intracellular T14-immunoreactive particles in adult brains, while acute silencing had no observable effect. In contrast, acute activation increased T14+ density in the STR, modified T14 puncta size near Rbp4Cre cell bodies in M1 layer 5 and their projections to the STR, and enhanced co-localisation of T14 with presynaptic terminals in the SN. Full article

Background/Objectives: As the regulatory center for basal ganglia, the substantia nigra is involved in the pathophysiology of dopaminergic dysregulation in Parkinson’s disease (PD). Increasing neuronal excitability of dopaminergic neurons by different therapeutic methods could reverse the locomotor disturbances of PD. The purpose of this study was the comparative assessment of effects induced by excitatory output from the motor cortex to the substantia nigra (SN) and to investigate the pattern of neuronal responses in an experimental rat model of rotenone-induced (intracerebral infusion) neurodegeneration and treated with bacterial melanin (BM). Methods: Thirty-three rats were divided into three groups: control or intact animals (n = 12), animals with the rotenone-induced model of PD (n = 10), and animals with the PD model and treated with BM in 48 h following the infusion (n = 11). Registration of neuronal activity from SN neurons was conducted at four weeks following the rotenone administration. High-frequency stimulation of brain cortical area M1 was performed and the background and evoked activity patterns of 622 neurons were recorded. The difference between the groups was analyzed using one-way ANOVA followed by Tukey’s test. Results: A statistically significant difference was observed between the similar proportions of post-stimulus effects registered in different groups, showing the predominance of excitatory responses in the neurons of the melanin-treated group. A comparison of the firing pattern between the SNc and SNr neurons did not reveal significant differences. Conclusions: BM treatment has the potential to enhance motor recovery after neurodegeneration in the SN. Deep brain stimulation via the cortico-nigral pathway, with the application of BM, enhances electrical activity in dopaminergic neurons of the substantia nigra and could be a potential therapeutic model for PD. Full article

Tree species composition, stand structure, and growth dynamics were evaluated within the priority habitat 91E0* (alluvial forests with Alnus glutinosa (L.) Gaertn., and Fraxinus excelsior L.) in the Nestos region of northeastern Greece. This study aimed to understand the ecological dynamics of this unique habitat and to properly plan restoration actions. Measurements were conducted in May and July 2023 across 14 plots distributed randomly along both banks of the Nestos River (east and west). A total of 667 trees with a DBH ≥ 2.5 cm were recorded, representing 13 species and 10 families. Tree densities ranged from 14 to 541 stems ha⁻¹, and the average basal area was 8.77 m² ha⁻¹. Both density and basal area significantly differed between the two riverbanks. Our results indicate that Alnus glutinosa dominates in the alluvial forest, forming more resilient communities with Populus alba L., Populus nigra L., and Salix alba L. However, Fraxinus angustifolia Vahl was not as prevalent as expected. These findings highlight the need for conservation actions and draw attention to the threats facing the alluvial forest. Full article

The pathogenesis of Parkinson’s disease (PD) consists of the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNpc) due to oxidative stress. The present study aimed to evaluate the potential antioxidant activity of whey protein isolate (WPI) in PD models, using neurotoxin-exposed SH-SY5Y cells differentiated into dopaminergic-like neurons. Our research shows that WPI’s high glutamic acid, aspartic acid, and leucine contribute to its antioxidant and neuroprotective effects, with glutamic acid crucial for glutathione synthesis. In vitro studies found that WPI, at concentrations of 5–1000 µg/mL, is non-toxic to differentiated SH-SY5Y cells. Notably, the lowest con-centration of WPI (5 µg/mL) significantly decreased intracellular reactive oxygen species (ROS) levels in these cells following a 24 h co-treatment with 1-methyl-4-phenylpyridinium (MPP⁺). The antioxidant effects of WPI were also confirmed by the increased expression of HO1 and GPx antioxidant enzymes, which are Nrf2 pathway target genes and were evaluated by real-time PCR. Furthermore, Nrf2 nuclear translocation in the differentiated SH-SY5Y cells was also increased when the cells were exposed to 5 µg/mL of WPI with MPP⁺. These results together suggest that WPI has antioxidant effects on dopaminergic-like neurons in a Parkinson’s disease model. Full article

Plant-derived foods have gained recognition for their health-promoting values, which are largely attributed to bioactive compounds such as phytosterols and triterpenoids. This study aimed to analyze the content of these compounds in the fruit of black elder (elderberry) Sambucus nigra L. and in commercially available food products, including jam, juice, syrup and wine. An additional objective was to compare the phytosterol and triterpenoid profiles of fruits and fruit cuticular waxes from wild and cultivated elderberry (cultivar Haschberg), ornamental elderberry (S. nigra f. porphyrophylla cultivar Black lace “Eva”), and red elderberry (S. racemosa). Qualitative and quantitative determinations were performed using gas chromatography coupled with mass spectrometry (GC-MS). This study provides a detailed characterization of triterpenoids in black and red elderberries, revealing a complex composition of oleanane-, 18-oleanane-, ursane-, lupane- and taraxastane-type compounds. Elderberry fruits were found to be rich sources of phytosterols (ranging from 0.54 mg/g d.w. in cultivated elderberry cv. Haschberg to 0.96 mg/g in ornamental elderberry) and triterpenoids (from 1.41 mg/g d.w. in S. racemosa to 13.81 mg/g in ornamental elderberry). Among the processed products, jam contained the highest concentration of these compounds (a total of 340 µg/g) and wine contained the lowest (0.87 µg/mL). Furthermore, the results suggest that certain features of the triterpenoid profile in S. nigra and S. racemosa may hold chemotaxonomic significance for the Sambucus genus. Full article

Background: Nardostachys jatamansi DC. (Gansong), a widely utilized herb in traditional Chinese medicine, has been historically employed in the management of various neuropsychiatric disorders. Nardosinone (Nar), a sesquiterpenoid compound, has been identified as one of the principal bioactive constituents of N. jatamansi. This study investigated the effects of ethyl acetate extract (NJ-1A) from N. jatamansi and its active constituent nardosinone on neuroinflammatory mediator release, glucose metabolic reprogramming, and T cell migration using both in vitro and in vivo experimental models. Methods: Lipopolysaccharide(LPS)-induced BV-2 microglial cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced male C57BL/6N mouse chronic model of Parkinson’s disease were applied. Results: Both NJ-1A and Nar could significantly suppress LPS-induced production of M1 pro-inflammatory factors or markers in microglia and could inhibit the glycolytic process and promote oxidative phosphorylation via the AKT/mTOR signaling pathway. Furthermore, they exhibited the capacity to attenuate chemokine release from activated microglia, consequently reducing T cell migration. In vivo experiments revealed that NJ-1A and Nar effectively inhibited microglial activation, diminished T cell infiltration, and mitigated the loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra of MPTP-induced mice. Conclusions: NJ-1A and nardosinone exert neuroprotective effects through the modulation of microglial polarization states, regulation of metabolic reprogramming, and suppression of T cell infiltration. Full article

Current studies suggest that environmental toxins may play a significant role in the fetal origins of Parkinson’s disease (PD). Significant evidence from animal experiments has demonstrated that these toxins can disrupt fetal neurodevelopment. PD is a neurodegenerative disorder related to the loss of dopaminergic neurons in the substantia nigra pars compacta (S. nigra) and accumulation of α-synuclein (α-syn) in the brain. Parkinson’s disease has long been associated with an idiopathic etiology, with environmental or ontogenetic factors as causes; however, the list of causal agents continues to expand as their effects are investigated at different stages of development. To explore the potential ontogenetic origins of PD, we exposed female rats subcutaneously (s.c.) to 1 mg/kg of the pesticide rotenone (ROT)—21 days during gestation, 21 days of breastfeeding, or 42 days in both periods—and assessed its long-term effects on their pups in adulthood. Our findings reveal that ROT exposure induces the degeneration of dopaminergic neurons in the S. nigra of adult rats. We administered ROT to dams during specific developmental stages and examined the nigrostriatal pathway and its functionality in offspring upon reaching young adulthood. Our results showed that perinatal ROT exposure led to (1) diminished motor skills, (2) greater concentrations of α-syn in the caudate nucleus (C. nucleus) and S. nigra, (3) reduced numbers of tyrosine hydroxylase immunoreactive neurons, and (4) hypomethylation of global 5-methylcytosine DNA compared to control rats at 60 days of age. The effects were more pronounced in rats exposed to ROT in utero and in both the in utero and breastfeeding periods, with fewer effects observed in those exposed only during breastfeeding. Thus, our findings suggest that exposure to ROT during the early developmental stages predisposes rats to Parkinsonian symptoms later in adulthood. Full article

Background/Objectives: The persistent threat of emerging respiratory RNA viruses like SARS-CoV-2 and Influenza A virus (IAV) necessitates the continuous development of effective, safe, broadly acting, and generally accessible antiviral agents. Current treatments often face limitations such as early administration requirements, resistance development, and limited global access. Natural products, like European black elderberry (Sambucus nigra L.; S. nigra) fruit extract and quinine, have been used historically against viral infections. In this study, we investigated the antiviral efficacy of a standardized black elderberry fruit extract containing 3.2% anthocyanins (EC 3.2) and, as a second natural antiviral product, quinine, against IAV and SARS-CoV-2 in vitro. Methods: Madin–Darby Canine Kidney II (MDCKII) cells were infected with IAV PR-8, while human Calu-3 lung epithelial cells were infected with Wuhan-type SARS-CoV-2. Cells were treated with varying concentrations of EC 3.2 and quinine either as mono- or combinational therapy. Viral replication was assessed using quantitative RT-PCR, and cell viability was evaluated using WST-1 assays. Results: Our results demonstrate, for the first time, that both EC 3.2 and quinine individually inhibited IAV replication in a dose-dependent manner, with IC₅₀ values of approximately 1:400 for EC 3.2 and 250 nM for quinine. Most importantly, the combinational treatment exhibited a strong synergistic antiviral effect, as confirmed by the Bliss independence model (synergy scores of 14.7 for IAV, and 27.8 for SARS-CoV-2), without affecting cell viability. Conclusions: These findings suggest that the combined use of black elderberry extract and quinine might serve as an effective antiviral strategy against IAV and SARS-CoV-2, particularly since the synergistic effect allows for lower doses of each product while retaining therapeutic efficacy. In summary, this combinational in vitro approach, when expanded to other respiratory RNA viruses and confirmed in clinical studies, has the potential to open a promising avenue for pandemic preparedness. Full article

Morus nigra L. is rich in anthocyanins and other active ingredients, but its extraction residues pose a burden on the environment. In the present study, Morus nigra L. extraction residue resource utilization was achieved through liquid fermentation of Schizophyllum commune, with the aim of enhancing anthocyanin solubilization and evaluating anti-inflammatory activity. Response surface methodology was used to optimize fermentation parameters and quantify anthocyanin fractions by HPLC. The anti-inflammatory effect was evaluated using the lipopolysaccharide-induced inflammation model of human foreskin fibroblast (BJ cell), and the interaction of cyanidin-3-O-glucoside (C3G) with NLRP3, a key target of the pyroptosis pathway, was resolved by molecular docking. Our results indicated that the optimal conditions (substrate 3.4%, inoculum 9%, time 50 h) enabled the total anthocyanin to reach 85.1 μg/mL, of which the C3G content was elevated to 66.7 μg/mL (release efficiency of 83.9%). The fermented filtrate effectively promoted BJ cell proliferation and inhibited the lipopolysaccharide-induced inflammatory response, with the pyroptosis signaling pathway playing a significant role. Molecular docking confirmed that C3G binds strongly to the NLRP3 protein. This technology provides a new strategy for high-value utilization of Morus nigra L. residues and the development of natural anti-inflammatory drugs. Full article

Natural extracts derived from plants have gained attention as potential therapeutic agents for obesity management. Some natural extracts were demonstrated to inhibit pancreatic lipase and alpha amylase, potentially influencing nutrient absorption and contributing to weight management. Pinus nigra subsp. laricio (Poir.) Maire, commonly known as the Calabrian pine or larch pine, is a subspecies of the black pine native to the mountains of southern Italy and Corsica. This study investigated the phytochemical content and antioxidant (DPPH and β-carotene bleaching assays) and enzymatic (lipase and amylase inhibition) activities of ethanolic extracts from apical shoots and branches, fractionated into n-hexane, dichloromethane, and ethyl acetate. All the extracts were also subjected to a preliminary evaluation of their anti-inflammatory potential by measuring the ability to inhibit nitric oxide (NO) production in RAW 264.7 macrophages. The ethyl acetate branch fraction exhibited the strongest antioxidant activity (DPPH IC50 15.67 ± 0.16 μg/mL), while the total branch extract best inhibited pancreatic lipase (IC50 0.62 mg/mL). Amylase inhibition was strongest in the ethyl acetate apical shoot fraction (IC50 22.05 ± 0.29 µg/mL). The branches’ hexane and dichloromethane fractions showed the greatest anti-inflammatory potential, inhibiting NO production in RAW 264.7 cells with IC50 values comparable to the positive control. Full article

Phenolic compounds are strong antioxidant and antibacterial agents with great pharmacological, medicinal, nutritional, and industrial value. The potential of Morus nigra in stem node culture was investigated for the production of phenolic compounds and their elicitation with CuSO₄. Individual phenolic compounds in the samples were identified and quantified by using HPLC-PDA and HPLC-MS methods, while the content of total phenolic compounds, the content of total flavonoids, and the antioxidant activity of methanolic extracts were evaluated spectrophotometrically. The highest fresh and dry weights were obtained in plantlets treated with 0.5 mM CuSO₄ for 42 days. The highest total phenolic content, total flavonoid content, and antioxidant activity of the extracts were determined in stem node cultures treated with 3 mM CuSO₄ for 42 days. Under the latter conditions, the predominant representatives of the caffeoylquinic acids, p-coumaric acid derivatives, kaempferol derivatives, and quercetin derivatives also achieved the highest content. The most abundant phenolic compound in all samples was the chlorogenic acid. The nodal culture of M. nigra elicited with CuSO₄ could potentially be used for the industrial production of phenolic compounds, especially caffeoylquinic acids. Moreover, considering the biochemical response to CuSO₄ treatment and the ability to tolerate and accumulate copper, the potential application of M. nigra in phytoremediation is also highlighted. Full article

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Constipation is a prodromal symptom of PD. It is important to investigate the pathogenesis of constipation symptoms in PD. Rotenone has been successfully used to establish PD animal models. However, the specific mechanism of rotenone-induced constipation symptoms is not well understood. In this work, we found that constipation symptoms appeared earlier than motor impairment in mice gavaged with a low dose of rotenone (30 mg/kg·BW). Rotenone not only caused loss of dopaminergic neurons and accumulation of α-synuclein, but also significantly reduced serum 5-HT levels and 5-HTR4 in the striatum and colon. The mRNA expression of aquaporins, gastrointestinal motility factors (c-Kit, Cx43, smMLCK and MLC-3) in mouse colon was also significantly regulated by rotenone. In addition, both colon and brain showed rotenone-induced inflammation and barrier dysfunction; the PI3K/AKT pathway in the substantia nigra and colon was also significantly inhibited by rotenone. Importantly, the structure, composition and function of the gut microbiota were also significantly altered by rotenone. Some specific taxa were closely associated with motor and constipation symptoms, inflammation, and gut and brain barrier status in PD mice. Akkermansia, Staphylococcus and Lachnospiraceae_UCG—006 may play a role in exacerbating constipation symptoms, whereas Acinetobacter, Lactobacillus, Bifidobacterium, Solibacillus and Eubacterium_xylanophilum_groups may be beneficial in stimulating gastrointestinal peristalsis, maintaining motor function and alleviating inflammation and barrier damage in mice. In conclusion, low-dose rotenone can cause parkinsonism with constipation symptoms in mice by disrupting the intestinal microecosystem and inhibiting the PI3K-AKT pathway and gastrointestinal motility. Full article