ORCID Profile
0000-0002-9910-0508
Current Organisation
Eberhard Karls Universität Tübingen
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Publisher: Springer Science and Business Media LLC
Date: 12-10-2023
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
Publisher: Elsevier BV
Date: 07-2018
Publisher: Springer Science and Business Media LLC
Date: 24-05-2019
DOI: 10.1007/S12031-019-01328-6
Abstract: In this study, we aimed to establish the effects of chronic corticosterone (CORT) and ethanol administration on mood-related behaviour and the levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor protein proBDNF in mice. C57BL6 male and female mice received drinking water (n = 22), 1% ethanol in drinking water (n = 16) or 100 μg/ml corticosterone in drinking water (containing 1% ethanol, n = 18) for 4.5 weeks. At the end of experimental protocol, the open field test (OFT) and elevated plus maze test were performed. Brain and adrenal tissues were collected and mBDNF and proBDNF were measured by ELISA assays. We found that the mice fed with corticosterone and ethanol developed anxiety-like behaviours as evidenced by reduced time in the central zone in the OFT compared with the control group. Both proBDNF and mBDNF were significantly decreased in the corticosterone and ethanol groups compared with the control group in the prefrontal cortex, hippoc us, hypothalamus and adrenal. The ratio of proBDNF/mBDNF in prefrontal cortex in the corticosterone group was increased compared with the ethanol group. Our data suggest that the ratio of proBDNF/mBDNF is differentially regulated in different tissues. Ethanol and corticosterone downregulate both mBDNF and proBDNF and alter the balance of proBDNF/mBDNF in some tissues. In conclusion, the ethanol and corticosterone may cause abnormal regulation of mBDNF and proBDNF which may lead to mood disorders.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.EXPNEUROL.2017.10.018
Abstract: Amyloid plaque is one of the hallmarks of Alzheimer's disease (AD). The key component beta-amyloid (Aβ) is generated via proteolytic processing of amyloid precursor protein (APP). Sortilin (encoded by the gene Sort1) is a vacuolar protein sorting 10 protein domain-containing receptor, which is up-regulated in the brain of AD, colocalizes with amyloid plaques and interacts with APP. However, its role in amyloidogenesis remains unclear. In this study, we first found that the protein level of sortilin was up-regulated in the neocortex of aged (7 and 9months old) but not young (2 and 5months old) AD mice (APP/PS1). 9months old APP/PS1 transgenic mice with Sort1 gene knockout showed increased amyloid pathology in the brain and this phenotype was rescued by intrahippoc al injection of AAV-hSORT1. Moreover, the 9months old APP/PS1 mice without Sort1 also displayed a decreased number of neurons and increased astrocyte activation in the hippoc us. In addition, the present study showed that the intracellular domain of sortilin was involved in the regulation of the non-specific degradation of APP. Together, our findings indicate that sortilin is a beneficial protein for the reduction of amyloid pathology in APP/PS1 mice by promoting APP degradation.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2018
DOI: 10.1007/S11064-017-2464-9
Abstract: Treatment with mature brain-derived neurotrophic factor (mBDNF) promotes functional recovery after ischemia in animal trials but the possible role of its precursor protein proBDNF and its receptors or the factors responsible for the conversion of proBDNF to mBDNF in ischemic stroke are not known. The main aim of this study was to characterize the time-dependent expression of genes and/or proteins related to BDNF processing and signaling after ischemia as well as the sensorimotor behavioral dysfunction in a photothrombotic ischemic model in rats. Characterization of different genes and proteins related to BDNF processing and signaling was performed using qPCR, immunoblotting and enzyme-linked immunosorbent assays. We showed in this study that some sensory and motor functional deficiencies appeared in the ischemic group at day 1 and persisted until day 14. Most changes in gene expression of BDNF and its processing enzymes occurred within the first 24 h in the ipsilateral cortex, but not in the contralateral cortex. At the protein level, proBDNF expression was increased at 6 h, mBDNF expression was increased between 15 h and 1 day while p75 receptor protein expression was increased between 6 h and 3 days in the ipsilateral cortex, but not in the contralateral cortex. Therefore, cerebral ischemia in rats led to the up-regulation of genes and/or proteins of BDNF, proBDNF and their processing enzymes and receptors in a time-dependent manner. We propose that the balance between BDNF and proBDNF and their associated proteins may play an important role in the pathogenesis and recovery from ischemia.
Publisher: FapUNIFESP (SciELO)
Date: 2022
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.NEURO.2018.02.013
Abstract: While people are often aware of the motor symptoms in Parkinson's disease (PD), few know of the many non-motor symptoms, which patients report have a greater impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the most common non-motor symptoms, which can occur at any stage of PD, even years prior to diagnosis, and can affect all sections along the GI tract causing a range of symptoms including drooling, gastroparesis and constipation. We have investigated whether a neurotoxin model of PD induced by rotenone, a mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction seen clinically. Sprague-Dawley rats were administered 2.75 mg/kg rotenone, 5 days/week for 4 weeks, via intraperitoneal injection. Rats underwent behavioural testing, including the one-hour stool and gastric emptying tests before GI contents and tissues were collected for microbiota and histological analysis. Rats exposed to rotenone had more days with evidence of diarrhoea and significantly delayed gastric emptying, reproducing the clinical symptom of gastroparesis. Microbiota analysis revealed alterations in the small intestine and colon of rotenone-treated rats, relatively consistent with changes described in PD patients. Histological analysis demonstrated mucosal thickening and goblet cell hyperplasia in the colon of rotenone rats, which may be an adaptive response to the toxin or changes in GI microbiota. Our results indicate that rotenone may be a good model for investigating the mechanisms involved with Parkinson's GI symptoms and for screening potential therapeutic options as it is capable of recapitulating some key GI changes that occur during PD progression.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Universidade Federal do Rio de Janeiro
Date: 22-12-2021
DOI: 10.11137/1982-3908_2021_44_43313
Abstract: This work aims to evaluate the potential for the debris-flow triggering from Santo Antônio hydrographic basin, located in the Serra do Mar region on North Coast of the State of São Paulo, Brazil, based on physiographic attributes, rainfall data, and morphometric parameters. For this purpose, hydrographic basin techniques were applied, assessing the vulnerability to the debris flow from geomorphological, geological, climatic, and anthropic aspects, and morphometric parameters relevant to the triggering of these processes in watersheds were calculated. Seven physiographic units were identified, which supported the understanding of geological and geomorphological aspects of the basin: coastal plains river plains colluvium and talus r s escarpments of Serra do Mar upland of Paraitinga mountainous relief and hillocks domain. The sub-basins located in steep sections of the relief, with high slopes, valleys, and channels docked, high drainage densities present higher values in the morphometric parameters, indicating a greater potential for triggering and occurrence of debris-flow processes. The joint analysis of physiographic compartmentalization with the identification of relief features, slope, litude, valley, slope shapes and morphometric parameters, is extremely relevant to recognize hydrographic basins susceptible to debris flows, as it integrates, and correlates aspects of the physical environment considered to trigger in the occurrence of these processes.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2023
Publisher: Revista Brasileira de Geomorfologia
Date: 06-04-2022
Abstract: The Serra do Mar mountain range is the main site of shallow-landslides occurrence in Brazil. The application of physically-based models is an effective method to predict landslide susceptibility, which is of great importance in hazard assessments and urban-planning studies. Thus, the objective of this study is to compare landslide susceptibility scenarios created with SHALSTAB and SINMAP at two large watersheds (Mogi and Perequê) in Cubatão, Latin America’s largest petrochemical site. Model calibration is based on the landslide scars inventory of the 1985 event, the geotechnical parameters derived from soil s les and the topography sourced from a 5 m resolution DEM. Using the Receiver Operating Characteristics (ROC) analysis to assess model performance, SHALSTAB emerges as the best-fit model for both watersheds due to higher concentration of landslide scars in unstable areas (true positive results) and higher global accuracy. Even though SINMAP had similar degree of success, it was slightly less accurate and failed more often in the identification of potentially unstable areas. Comparative performance studies of physically-based models are fundamental to support effective and reliable hazard assessments in mountain regions, providing an outlook in how to proceed with more detailed studies.
Publisher: Informa UK Limited
Date: 06-02-2019
Publisher: Springer International Publishing
Date: 23-12-2021
Publisher: Springer Science and Business Media LLC
Date: 04-06-2018
DOI: 10.1038/S41380-018-0071-Z
Abstract: Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3β pathway. Genetic reduction of p75NTR in P301L mice rescued the memory deficits, alleviated tau hyperphosphorylation and restored the activity of the AKT/GSK3β pathway. Treatment of the P301L mice with the soluble p75NTR extracellular domain (p75ECD-Fc), which can antagonize neurotoxic ligands of p75NTR, effectively improved memory behavior and suppressed tau pathology. This suggests that p75NTR plays a crucial role in tau paGSKthology and represents a potential druggable target for FTLD-tau and related tauopathies.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2018
DOI: 10.1007/S12035-018-1106-9
Abstract: The accumulation of excess intracellular or extracellular amyloid beta (Aβ) is one of the key pathological events in Alzheimer's disease (AD). Aβ is generated from the cleavage of amyloid precursor protein (APP) by beta secretase-1 (BACE1) and gamma secretase (γ-secretase) within the cells. The endocytic trafficking of APP facilitates amyloidogenesis while at the cell surface, APP is predominantly processed in a non-amyloidogenic manner. Several adaptor proteins bind to both APP and BACE1, regulating their trafficking and recycling along the secretory and endocytic pathways. The phosphorylation of APP at Thr668 and BACE1 at Ser498, also influence their trafficking. Neurotrophins and proneurotrophins also influence APP trafficking through their receptors. In this review, we describe the molecular trafficking pathways of APP and BACE1 that lead to Aβ generation, the involvement of different signaling molecules or adaptor proteins regulating APP and BACE1 subcellular localization. We have also discussed how neurotrophins could modulate amyloidogenesis through their receptors.
Publisher: Springer Science and Business Media LLC
Date: 13-12-2022
DOI: 10.1007/S10346-022-01984-7
Abstract: This study aims at providing an overview of the socioeconomic consequences that debris-flow events have caused in Brazil, positioning the country in the international scenario and identifying areas where targeted actions are necessary. The analysis is conducted by calculating the debris-flow mortality rate (MR) and by using the so-called F-N plots (frequency of events that have caused N or more fatalities vs. the number of fatalities), based on a compilation of debris-flow-related disasters from 1920 to 2021. In total, 45 debris-flow events were documented in the considered period, responsible for 5771 fatalities and more than 5.5 billion USD in economic losses. The Serra do Mar Mountain Range is the main site of reported debris-flow occurrences (64.5%), followed by Serra da Mantiqueira (13.3%), and Serra Geral (13.3%). Southeast Brazil (SEB) is the region most affected by debris-flow events, due to the highest population density and the development of several cities in hilly areas, such as Petrópolis (Rio de Janeiro state) and Cubatão (São Paulo state). The debris-flow MR of SEB is higher than any other region in Brazil, pushing the national debris-flow MR upwards, and the F-N curve of SEB consolidates the region as the one with the highest risk to the phenomenon, indicating a higher probability of fatal events. The F-N plots further show that debris-flow events in Brazil represent a higher societal risk than in countries such as China, Japan and Italy. While there are differences in country size and the scale effect should be considered, these results highlight the urgent need for investments in disaster prevention and preparedness programs.
Publisher: Impact Journals, LLC
Date: 03-09-2019
Publisher: Copernicus GmbH
Date: 23-03-2020
DOI: 10.5194/EGUSPHERE-EGU2020-3706
Abstract: & & & span& Debris flows represent great hazard to communities and infrastructures, since they move quickly and are very destructive. In Brazil, debris flows mainly occur in the Serra do Mar Mountain Range, where thousands of casualties were reported in the last two decades due to these phenomena. This study aims at estimating the magnitude of a debris-flow event that occurred in Serra do Mar on February 2017, at the Pedra Branca watershed in the State of Paran& #225 . Debris-flow magnitude refers to the volume of material discharged during an event and is an important aspect of debris-flow hazard assessment. The Pedra Branca event was initiated by rainfall-triggered shallow landslides, damaging local oil pipelines and farms. The magnitude estimation is based on the combination of empirically based equations and the geomorphic features of the debris flow, acquired from & em& in situ& /em& and aerial investigation. 28 cross-sections were made along the river channel, considering post-event channel width, erosion and accumulation depth, as well as depositional features. Sediment sources and accumulation areas were identified and delimitated based on high-resolution (1:500) aerial drone photographs. The results indicate that the landslides that initiated the event released approximately 26,884.5 m& sup& & /sup& of sediments (V& sub& i& /sub& ) into the main channel of Pedra Branca and that the volume eroded (V& sub& e& /sub& ) and accumulated (V& sub& d& /sub& ) along the channel are, respectively, 82,439 m& sup& & /sup& and 22,012 m& sup& & /sup& . The estimated total solids volume (V& sub& s& /sub& ) is 87,274 m& sup& & /sup& , assuming that V& sub& s& /sub& = V& sub& i& /sub& + V& sub& e& /sub& - V& sub& d& /sub& . Moreover, considering a solids concentration of 57% calculated according to empirically-based equations for Serra do Mar, the debris flow had a total magnitude of 153,113 m& sup& & /sup& . These estimations suggest that the February 2017 debris flow mobilised great volume of material and that 15% of the total volume accumulated on the channel bed, which can be remobilised by future events. Further research on debris-flow dynamics and recurrence at the Serra do Mar Mountain Range is recommended to mitigate future hazards.& /span& & &
Publisher: Elsevier BV
Date: 12-2021
Publisher: OMICS Publishing Group
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 30-05-2021
DOI: 10.1007/S11069-021-04811-9
Abstract: Debris flows represent great hazard to humans due to their high destructive power. Understanding their hydrogeomorphic dynamics is fundamental in hazard assessment studies, especially in subtropical and tropical regions where debris flows have scarcely been studied when compared to other mass-wasting processes. Thus, this study aims at systematically analyzing the meteorological and geomorphological factors that characterize a landslide-triggered debris flow at the Pedra Branca catchment (Serra do Mar, Brazil), to quantify the debris flow’s magnitude, peak discharge and velocity. A magnitude comparison with empirical equations (Italian Alps, Taiwan, Serra do Mar) is also conducted. The meteorological analysis is based on satellite data and rain gauge measurements, while the geomorphological characterization is based on terrestrial and aerial investigations, with high spatial resolution. The results indicate that it was a large-sized stony debris flow, with a total magnitude of 120,195 m 3 , a peak discharge of 2146.7 m 3 s −1 and a peak velocity of 26.5 m s −1 . The debris flow was triggered by a 188-mm rainfall in 3 h (maximum intensity of 128 mm h −1 ), with an estimated return period of 15 to 20 years, which, combined with the intense accumulation of on-channel debris (ca. 37,000 m 3 ), indicates that new high-magnitude debris flows in the catchment and the region are likely to occur within the next two decades. The knowledge of the potential frequency and magnitude ( F – M ) can support the creation of F – M relationships for Serra do Mar, a prerequisite for reliable hazard management and monitoring programs.
Publisher: Instituto de Geociencias - UFRJ
Date: 09-08-2019
Publisher: Springer Science and Business Media LLC
Date: 27-03-2019
DOI: 10.1007/S12640-019-00022-0
Abstract: Stroke is accompanied by severe inflammation in the brain. The role of mature brain-derived neurotrophic factor (mBDNF) in ischemic stroke has received intensive attention, but the function of its precursor proBDNF is less understood. Recent studies showed that mBDNF and proBDNF in the ischemic brain are upregulated, but the significance of mBDNF and proBDNF in the lymphocytes in ischemic stroke is not known. Here, we propose that the expression levels of mBDNF and proBDNF in lymphocytes correlate with those in the brain after ischemic stroke and therefore can be surrogate markers for the ischemic brain. Using a photothrombotic model in rats and ELISA assay technique, we found that proBDNF and mBDNF in peripheral lymphocytes were upregulated but produced differential time courses after ischemia. The levels of mBDNF and proBDNF in lymphocytes at early stages of stroke (1 day), showed a strong positive correlation with those in the brain. The levels of p75, sortilin, were also increased in a time-dependent manner after ischemic stroke however, the levels of p-TrkB in the ischemic brain at 6 h, 1 and 3 days were significantly reduced in the brain. The present study suggests that the levels of proBDNF and mBDNF in the blood lymphocytes in acute ischemic stroke reflect those in the brain at early stages.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2017
Location: Brazil
No related grants have been discovered for Victor Carvalho Cabral.