Biological Research最新文献

{"title":"A snapshot of cancer in Chile II: an update on research, strategies and analytical frameworks for equity, innovation and national development.","authors":"Cristóbal Vacarezza, Julieta Araneda, Pamela Gonzalez, Oscar Arteaga, Katherine Marcelain, Enrique A Castellon, Ana Periera, Maroun Khoury, Bettina Müller, Juan Alberto Lecaros, Sofia P Salas, Arnoldo Riquelme, Alejandro H Corvalan, Jorge Jiménez de la Jara, Catterina Ferreccio, Carolina Goic, Bruno Nervi, Juan Carlos Roa, Gareth I Owen","doi":"10.1186/s40659-024-00574-2","DOIUrl":"10.1186/s40659-024-00574-2","url":null,"abstract":"<p><strong>Introduction: </strong>Chile has achieved developed nation status and boasts a life expectancy of 81 + years; however, the healthcare and research systems are unprepared for the social and economic burden of cancer. One decade ago, the authors put forward a comprehensive analysis of cancer infrastructure, together with a series of suggestions on research orientated political policy.</p><p><strong>Objectives: </strong>Provide an update and comment on policy, infrastructure, gender equality, stakeholder participation and new challenges in national oncology. Assess the funding and distribution of cancer investigation. Present actions for the development of oncology research, innovation and patient care.</p><p><strong>Methods: </strong>Triangulating objective system metrics of economic, epidemiological, private and public sector resources together with policy analysis, we assessed cancer burden, infrastructure, and investigation. We analyzed governmental and private-sector cancer databases, complemented by interviews with cancer stakeholders.</p><p><strong>Results: </strong>Governmental policy and patient advocacy have led to the recognition of cancer burden, a cancer law, and a national cancer plan. Cancer has become the leading cause of death in Chile (59,876 cases and 31,440 cancer deaths in 2022), yet only 0.36% gross domestic product (GDP) is directed to research and development. Inequalities in treatment regimens persist. Prevention policy has lowered tobacco consumption, sugar intake via soft drinks and offered a high coverage of HPV vaccines. A high-quality cancer research community is expanding, and internationally sponsored clinical oncology trials are increasing.</p><p><strong>Conclusions: </strong>The cancer law has facilitated advancement in policy. Prevention policies have impacted tobacco and sugar intake, while gender equality and care inequality have entered the public forum. Cancer research is stagnated by the lack of investment. Implementation of a cancer registry and biobanking, reinforcement of prevention strategies, development of human resources, promotion of clinical trial infrastructure and investment in new technologies must be placed as a priority to permit advancements in innovation and equitable cancer care.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"95"},"PeriodicalIF":4.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-base deletion in exon 2 of Hd1 delineates monogenic recessive photoperiod insensitivity in aromatic Joha rice: a novel allele for seasonal adaptability.","authors":"Bodeddula Jayasankar Reddy, Shreekant M Baradkar, Tamma V S S Manogna, Dibosh Bordoloi, Subhash C Bihani, Nagendra Sarma Barua, Akhil Ranjan Baruah, Bikram Kishore Das, Suvendu Mondal, Debojit Sarma","doi":"10.1186/s40659-024-00553-7","DOIUrl":"10.1186/s40659-024-00553-7","url":null,"abstract":"<p><strong>Background: </strong>Assam's aromatic Joha rice is a unique rice class famous for its aroma, taste, and nutritional benefits, which fetch high market prices in domestic and international markets. Joha landraces are inherently poor yielders due to their strong aroma and predominantly photoperiod sensitivity. Hybridization involving non-aromatic HYVs improves yield with concomitant loss of quality. In this context, mutation breeding, a sustainable approach where genetic mutations are induced to create desirable traits, often provides useful allelic variation in specific morpho-agronomic traits. The present study delves into the genetic characterization of a photoperiod-insensitive mutant. As part of our mutation breeding programme, this mutant was isolated from a gamma ray-induced M₂ population of a Joha rice landrace, Kon Joha.</p><p><strong>Results: </strong>The mutant was unique, and a single recessive gene conditions the induced photoperiod insensitivity. Mutant gene tagging involved 402 SSR and InDel markers, and later polymorphic markers were used for bulk segregant analysis (BSA) in the F2 population of 'mutant × Kalijeera (distant parent)'. BSA revealed an association between the SSR marker RM527 and this mutant trait. This marker is present on chromosome 6 of the rice genome. Using chromosome 6-specific SSR markers in polymorphic screening and BSA revealed another associated marker, RM19725, for the mutant trait. The genomic interval between RM527 and RM19725 harbors a photoperiod-insensitive gene, Hd1, on chromosome 6. Cloning and sequencing of Hd1 genomic fragments from the parents and mutants revealed a single-base deletion in exon 2, leading to a frameshift mutation in the Hd1 protein. This mutation in exon 2 leads to severe structural abnormalities in the CCT domain of the Hd1 protein that is critical for the interaction of the repressing complex with conserved response elements in the florigen gene under long-day conditions, thereby causing photoperiod insensitivity.</p><p><strong>Conclusions: </strong>The mutant's pleasant aroma and other quality characteristics, comparable to those of the parent cultivar, hold significant promise. They expand its potential use in a structured breeding programme aimed at developing high-value aromatic Joha rice. This rice, resilient to winter- and summer-growing environments and with broad seasonal adaptability, could revolutionize the rice market. The practical value of our research is underscored by this exciting possibility.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"94"},"PeriodicalIF":4.3,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity in the formation of primary and secondary visual fields during human prenatal development.","authors":"Olga Godovalova, Alexandra Proshchina, Anastasia Kharlamova, Valeriy Barabanov, Yuliya Krivova, Olga Junemann, Marina Shahina, Sergey Saveliev","doi":"10.1186/s40659-024-00576-0","DOIUrl":"10.1186/s40659-024-00576-0","url":null,"abstract":"<p><p>The human neocortex has a huge surface area with unique cytoarchitectonics, most of which is concealed in sulci. Some cytoarchitectonic fields are associated with macroscopic landmarks. In particular, the primary visual field 17 is associated with the calcarine sulcus. During the prenatal development of the human brain, neocortical gyri and sulci undergo changes and modifications after primary formation. To explore the morphogenetic processes in visual fields during the formation of the primary (provisional) and secondary (permanent) sulci, the occipital lobe of the human fetal brain was studied using immunohistochemical methods. The distribution of various glial and neuronal markers (S-100, β-III-tubulin, NeuN, reelin) in the calcarine sulcus and parietooccipital sulcus was compared. The heterogeneity in the formation of primary and secondary visual fields was demonstrated. The study revealed that the development of the primary visual field 17, linked with the calcarine sulcus, preceded the development of a shared anlage of fields 18 and 19 linked with the parietooccipital sulcus. The functional differentiation of the primary visual field begins during the period of thalamic afferent ingrowth. This process coincides with the temporal smoothing of the calcarine sulcus, indicating a simultaneous progression of functional specialization and structural modifications. At the late fetal period, cortical plate of gyri and sulci banks showed higher NeuN-labeling than inside the sulcus in the same cytoarchitectonic field.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"93"},"PeriodicalIF":4.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress drives premature hive exiting behavior that leads to death in young honey bee (Apis mellifera) workers.","authors":"Jordan Twombly Ellis, Juliana Rangel","doi":"10.1186/s40659-024-00569-z","DOIUrl":"10.1186/s40659-024-00569-z","url":null,"abstract":"<p><strong>Background: </strong>The Western honey bee, Apis mellifera, is an economically important pollinator, as well as a tractable species for studying the behavioral intricacies of eusociality. Honey bees are currently being challenged by multiple biotic and environmental stressors, many of which act concomitantly to affect colony health and productivity. For instance, developmental stress can lead workers to become precocious foragers and to leave the hive prematurely. Precocious foragers have decreased flight time and lower foraging efficiency, which can ultimately lower colony productivity and even lead to colony collapse.</p><p><strong>Materials and methods: </strong>In this study, we tested the hypothesis that stress during pupal development can cause young workers to exit the hive prematurely before they are physically able to fly. This premature exiting behavior results in death outside the hive soon thereafter. To determine how various stressors may lead bees to perform this behavior, we subjected workers during the last pupal stage to either cold stress (26 °C for 24 h), heat stress (39 °C for 24 h), or Varroa destructor mite parasitization, and compared the rate of premature hive exits between stressed bees and their respective control counterparts. Upon emergence, we individually tagged focal bees in all treatment groups and introduced them to a common observation hive. We then followed tagged bees over time and monitored their survivorship, as well as their likelihood of performing the premature hive exiting behavior. We also dissected the hypopharyngeal glands of all treatment and control bees sampled.</p><p><strong>Results: </strong>We found that significantly more bees in all three treatment groups exited the hive prematurely compared to their control counterparts. Bees in all treatment groups also had significantly smaller hypopharyngeal glands than control bees.</p><p><strong>Conclusions: </strong>Our results suggest that premature hive exiting behavior is driven by stress and is potentially a form of accelerated age polyethism that leads to premature death.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"92"},"PeriodicalIF":4.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female prediabetic rats are protected from vascular dysfunction: the role of nitroso and sulfide signaling.","authors":"Sona Cacanyiova, Andrea Berenyiova, Hana Malinska, Martina Huttl, Irena Markova, Basak G Aydemir, Veronika Garaiova, Martina Cebova","doi":"10.1186/s40659-024-00575-1","DOIUrl":"10.1186/s40659-024-00575-1","url":null,"abstract":"<p><strong>Background: </strong>The activity of perivascular adipose tissue (PVAT), a specific deposit of adipose tissue surrounding blood vessels, could contribute to sex differences in vascular tone control, particularly in dyslipidemic disorders; however, the mutual associations remain unclear. This study aimed to evaluate the relationships among sex, PVAT and vascular function in Wistar and hereditary hypertriglyceridemic (HTG) rats. Vasoactive responses of the isolated thoracic aorta with preserved or removed PVAT were compared in adult male and female Wistar and HTG rats, and the roles of nitric oxide (NO), hydrogen sulfide (H₂S), cyclooxygenase (COX) and inflammatory signaling in vascular function were monitored in females.</p><p><strong>Results: </strong>HTG rats were hypertensive, but females less than males. Increased 2-h glycemia was observed in HTG rats regardless of sex; however, HTG females exhibited better glucose utilization than males did. Females, independent of strain, had better preserved endothelial function than males did. PVAT inhibited endothelium-dependent relaxation in all the rats except HTG females. In HTG males, pathologically increased aortic contractility was noted; however, in HTG females, the contractile responses were lower, thus approaching physiological levels despite the pro-contractile action of COX products. In HTG females, NO contributed to endothelial function to a lesser extent than it did in controls, but the presence of PVAT eliminated this difference, which corresponded with increased NO synthase activity. Although increased protein expression of several proinflammatory factors (TNFα, IL-6, iNOS, and NfκB) was confirmed in the aortic and PVAT tissue of HTG females, the protein expression of factors regulating the adhesion and infiltration of monocytes (ICAM-1 and MCP-1) was decreased in PVAT. Moreover, in HTG females, unlike in controls, H₂S produced by PVAT did not inhibit endothelial relaxation, and regardless of PVAT, endogenous H₂S had beneficial anticontractile effects, which were associated with increased protein expression of H₂S-producing enzymes in both aortic and PVAT tissues.</p><p><strong>Conclusions: </strong>Despite increased inflammation and the pathological impact of cyclooxygenase signaling in female HTG rats, protective vasoactive mechanisms associated with milder hypertension and improved endothelial function and contractility linked to PVAT activity were triggered. Sulfide and nitroso signaling represent important compensatory vasoactive mechanisms against hypertriglyceridemia-associated metabolic disorders and may be promising therapeutic targets in prediabetic females.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"91"},"PeriodicalIF":4.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.","authors":"Huan-Yu Zhao, Yi-Pan Zhu, Ying Wen, Jing Sun, Xin-Yu Ding, Xin-Yu Cao, Kai-Liang Wu, Li Fu, Lu-Yuan Li","doi":"10.1186/s40659-024-00566-2","DOIUrl":"10.1186/s40659-024-00566-2","url":null,"abstract":"<p><strong>Background: </strong>The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations.</p><p><strong>Results: </strong>Protein kinase C isoform ζ (PKCζ), which is highly expressed in breast cancer cells, accumulates in the nuclei of human mammary epithelial cells overexpressing human rhomboid family-1 (RHBDF1), an endoplasmic reticulum membrane protein. Nuclear translocation of PKCζ results in the failure of the formation of the cytosolic apicobasal polarity complex Par, of which PKCζ is an essential component. Additionally, enhanced nuclear translocation of PKCζ is accompanied by an inhibition of the expression of cell tight junction and adherens junction proteins and an increase of cell mobility. Mechanistically, RHBDF1 is able to interact with importin β1 and PKCζ and promote PKCζ phosphorylation. Consistently, treatment of RHBDF1-overexpressing cells with an inhibitor of PKCζ phosphorylation leads to restoration of apicobasal polarity and cell-cell junctions, as well as suppressed cell mobility.</p><p><strong>Conclusions: </strong>RHBDF1-facilitated nuclear translocation of PKCζ is critically responsible for the dismantlement of epithelial cell apicobasal polarity, and thus may serve as a target in the development of therapeutic approaches against early stages of breast cancer.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"90"},"PeriodicalIF":4.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the therapeutic potential of induced neural stem cells for Alzheimer's disease in mice.","authors":"Qiongqiong Ji, Yuanhao Lv, Bei Hu, Yue Su, Imran Ibrahim Shaikh, Xu Zhu","doi":"10.1186/s40659-024-00568-0","DOIUrl":"10.1186/s40659-024-00568-0","url":null,"abstract":"<p><p>Induced neural stem cells (iNSCs), which have similar properties to neural stem cells and are able to self-proliferate and differentiate into neural cell lineages, are expected to be potential cells for the treatment of neurodegeneration disease. However, cell therapy based on iNSCs transplantation is limited by the inability to acquire sufficient quantities of iNSCs. Previous studies have found that mouse and human fibroblasts can be directly reprogrammed into iNSCs with a single factor, Sox2. Here, we induced mouse embryonic fibroblasts (MEFs) into iNSCs by combining valproic acid (VPA) with the induction factor Sox2, and the results showed that VPA significantly improved the conversion efficiency of fibroblasts to iNSCs. The iNSCs exhibited typical neurosphere-like structures that can express NSCs markers, such as Sox2, Nestin, Sox1, and Zbtb16, and could differentiate into neurons, astrocytes, and oligodendrocytes in vitro. Subsequently, the iNSCs were stereotactically transplanted into the hippocampus of APP/PS1 double transgenic mice (AD mice). Post-transplantation, the iNSCs showed long-term survival, migrated over long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Importantly, the cognitive abilities of APP/PS1 mice transplanted with iNSCs exhibited significant functional recovery. These findings suggest that VPA enhances the conversion efficiency of fibroblasts into iNSCs when used in combination with Sox2, and iNSCs hold promise as a potential donor material for transplantation therapy in Alzheimer's disease.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"89"},"PeriodicalIF":4.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of chronic exogenous oxytocin administration on exercise performance and cardiovagal control in hypobaric hypoxia in rats.","authors":"Camila Salazar-Ardiles, Carlos Cornejo, Cristobal Paz, Manuel Vasquez-Muñoz, Alexis Arce-Alvarez, Maria Rodriguez-Fernandez, Gregoire P Millet, Mikel Izquierdo, David C Andrade","doi":"10.1186/s40659-024-00573-3","DOIUrl":"10.1186/s40659-024-00573-3","url":null,"abstract":"<p><strong>Background: </strong>Outstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats.</p><p><strong>Results: </strong>A vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO₂: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups.</p><p><strong>Conclusion: </strong>The findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"88"},"PeriodicalIF":4.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: a new in vivo model of neurodegeneration.","authors":"Md Samsuzzaman, Seong-Min Hong, Jae Hyuk Lee, Hyunjun Park, Keun-A Chang, Hyun-Bum Kim, Myoung Gyu Park, Hyeyoon Eo, Myung Sook Oh, Sun Yeou Kim","doi":"10.1186/s40659-024-00572-4","DOIUrl":"10.1186/s40659-024-00572-4","url":null,"abstract":"<p><strong>Background: </strong>Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear.</p><p><strong>Results: </strong>We investigated the effect of MGO stress on depression like-behavior and memory loss to elucidate the potential interplay between MGO-induced tryptophan (Trp) metabolism impairment and oxidative stress in the brain. It demonstrates that MGO induces depression-like behavior in mice, as confirmed by the OFT, TST, FST, SPT, and EPM behavioral tests. MGO led to the depletion of Trp and related neurotransmitters as 5-HT, EPI, and DA in the mouse brain. Additionally, MGO reduced the cell count in the DG, CA1, and CA3 hippocampal regions and modulated TPH2 levels in the brain. Notably, co-treatment with MGO and Trp mirrored the effects observed after Trp-null treatment in neurons, including reduced TPH1 and TPH2 levels and inhibition of neuronal outgrowth. Furthermore, MGO significantly altered the expression of key proteins associated with neurodegeneration, such as p-Tau, p-GSK-3β, APP, oAβ, BDNF, NGF, and p-TrkB. Concurrently, MGO activated MAPKs through ROS induction, triggering a redox imbalance by downregulating Nrf-2, Ho-1, TXNRD1, Trx, Sirt-3, and Sirt-5 expression levels, NAD^+, and CAT activity in the mouse brain. This led to an accelerated neuroinflammatory response, as evidenced by increased expression of Iba-1, p-NF-κB, and the secretion of IL-6 and TNF-α. Importantly, Trp treatment ameliorated MGO-induced depression like-behavior and memory loss in mice and markedly mitigated increased expression of p-Tau, APP, p-ERK1/2, p-pJNK, and p-NF-κB in the brain. Likewise, Trp treatment also induced the expression of MGO detoxifying factors GLO-I and GLO-II and CAT activity, suggesting the induction of an antioxidant system and reduced inflammation by inhibiting IL-6 and TNF-α secretion.</p><p><strong>Conclusions: </strong>Our data revealed that MGO-induced depression like-behavior and memory deficits resulted from disturbances in Trp, 5-HT, BDNF, and NGF levels, increased p-Tau and APP expression, neuroinflammation, and impaired redox status (Nrf-2/Ho-1/TXNRD1/Sirt3/5) in the brain.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"87"},"PeriodicalIF":4.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of autophagy enhancer PACER/RUBCNL in neurons accelerates disease in the SOD1^G93A ALS mouse model.","authors":"Luis Labrador, Leonardo Rodriguez, Sebastián Beltran, Fernanda Hernandez, Laura Gomez, Patricia Ojeda, Cristian Bergmann, Melissa Calegaro-Nassif, Bredford Kerr, Danilo B Medinas, Patricio Manque, Ute Woehlbier","doi":"10.1186/s40659-024-00567-1","DOIUrl":"10.1186/s40659-024-00567-1","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal paralytic disorder associated with motor neuron death. Mutant superoxide dismutase 1 (SOD1) misfolding and aggregation have been linked to familial ALS, with the accumulation of abnormal wild-type SOD1 species being also observed in postmortem tissue of sporadic ALS cases. Both wild-type and mutated SOD1 are reported to contribute to motoneuron cell death. The autophagic pathway has been shown to be dysregulated in ALS. Recent evidence suggests a dual time-dependent role of autophagy in the progression of the disease. PACER, also called RUBCNL (Rubicon-like), is an enhancer of autophagy and has been found diminished in its levels during ALS pathology in mice and humans. Pacer loss of function disturbs the autophagy process and leads to the accumulation of SOD1 aggregates, as well as sensitizes neurons to death. Therefore, here we investigated if constitutive overexpression of PACER in neurons since early development is beneficial in an in vivo model of ALS. We generated a transgenic mouse model overexpressing human PACER in neurons, which then was crossbred with the mutant SOD1^G93A ALS mouse model. Unexpectedly, PACER/SOD1^G93A double transgenic mice exhibited an earlier disease onset and shorter lifespan than did littermate SOD1^G93A mice. The overexpression of PACER in neurons in vivo and in vitro increased the accumulation of SOD1 aggregates, possibly due to impaired autophagy. These results suggest that similar to Pacer loss-of function, Pacer gain-of function is detrimental to autophagy, increases SOD1 aggregation and worsens ALS pathogenesis. In a wider context, our results indicate the requirement to maintain a fine balance of PACER protein levels to sustain proteostasis.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"86"},"PeriodicalIF":4.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}