A randomised trial of short- vs long-term androgen deprivation with salvage radiotherapy for biochemical failure following radical prostatectomy: URONCOR 06-24.

BACKGROUND: Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. STUDY DESIGN: The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). ENDPOINTS: The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life. METHODS AND ANALYSIS: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. ETHICS AND DISSEMINATION: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT number 2021-006975-41.

Epidemiological profile of malaria in a rural community in the Amazon, Mato Grosso State, Brazil, 2011.

BACKGROUND: More than 95% of malaria transmission in Brazil occurs in the Legal Amazon Region, which in 2010 recorded around 333,429 cases reported in the Epidemiological Surveillance Information System-Malaria (Sivep_malaria), presenting an annual parasitic incidence (IPA) of 13.1 cases/1000 inhabitants. METHODS: This was a descriptive study that measured the community prevalence of Plasmodium infection and its relationship with land use in Três Fronteiras District, Colniza Municipality, Mato Grosso State. Data were collected during household visits in July 2011, with blood collection from finger pricks for the preparation of thick smear slides, and completion of a standardized case notification form. A georeferenced database was analysed, with land use evaluated as categorical variables. A kernel density map was built to show the density of cases and their location. RESULTS: Of the 621 respondents, 68(11%) had Plasmodium infection: 39 (57.4%) with Plasmodium vivax, 27(39.7%) with Plasmodium falciparum and two (2.9%) with mixed infections. Among infected individuals, 49 (72.1%) were men. Cases of malaria were distributed over the district, with greater occurrence of cases per household in open areas close to the mining company and artisanal mining sites. The was a greater density of cases located in the gold mining region. CONCLUSION: Transmission of malaria in Três Fronteiras District has a heterogeneous distribution. Individuals residing in mining and timber extraction sites have increased occurrence of Plasmodium infection.

Feeding protocol with live feed and inert diet to determine the ideal age/size for weaning mullet Mugil liza (Valenciennes, 1836).

The Lebranche mullet Mugil liza is a marine fish of great importance for artisanal and industrial fishing, as well as aquaculture. The use of live feeds during the larviculture phase of marine fish is a significant component of production costs. The present study evaluated the effects of the feeding transition on different larval stages of M. liza, from the combined supply of live feed (Brachionus rotundiformis + Artemia franciscana) and live + inert feed (Artemia franciscana + inert diet) until the weaning phase to only the inert diet. A total of 3240 M. liza larvae (weight 0.0133 ± 0.0062 g and length 0.793 ± 0.160 cm) were distributed among the 12 experimental units (n = 270), resulting in four groups with three replicates each. Treatment groups consisted of feed transition with A. franciscana (enriched metanauplii) to commercial inert feed starting weaning at four different larval ages: 28, 31, 34, and 37 days post hatching. Zootechnical performance indexes and intestinal histomorphometry were evaluated. Mortality, condition factor, and length variation coefficient did not show significant differences between treatments. Final weight, final length, weight gain, and length gain were significantly greater in larvae that started weaning at 31, 34, and 37 days post hatching. Weight coefficient of variation was significantly higher in larvae that started weaning at 28 days (67.51 ± 11.70) compared to 37 days (34.40 ± 7.30). In intestinal histology, villi height (180.3 ± 4.4) was significantly higher in larvae that started weaning at 37 days post hatching. Considering the evidence found in the present study, it is recommended to start weaning M. liza on the 31st day post-hatching, using a 2-day co-feeding protocol (31st and 32nd days). From the 33rd day after hatching, M. liza larvae can receive only commercial feed.

Comparative analysis indicates a simple protocol for DNA extraction of the aromatic plant Lippia alba.

An efficient method of genomic DNA extraction that provides high quality and yield is a crucial pre-requisite and limiting factor in plant genetic analysis. However, pure genomic DNA can be challenging to obtain from some plant species due to their sugar and secondary metabolite contents. Lippia alba is an important aromatic and medicinal plant, chemically characterized by the presence of tannins, flavonoids, anthocyanins, and essential oils, which interfere with the extraction of pure genomic DNA. In this scenario, optimizing the extraction methods and minimizing the effects of these compounds are necessary. This study compares six plant DNA extraction protocols based on the CTAB method. The quality and quantity of DNA samples obtained were determined by physical appearance by electrophoresis in agarose gels and spectrophotometry. The results highlight the difficulty in obtaining pure and clear bands for all tested methods, except for the polyvinylpyrrolidone (PVP)-based protocol created by our team, which was the better option for obtaining high-quality genomic DNA of L. alba. We conclude that adding PVP-40 into DNA extraction buffers can optimize the DNA extraction of L. alba and indicate this protocol for DNA extraction from other aromatic plants.

Phosphorus in alkaline soils of the semiarid region, Brazil: inorganic fractions, capacity factor, and availability.

The study was designed to quantify the contents of Pi fractions and correlate them with the P capacity factor of soils in the Brazilian semiarid region. We also evaluated the effect of soil P doses contact time and P availability for maize plants in alkaline soils of the Brazilian semiarid region. Soil samples were collected between the Piranhas-Açu (RN) and Jaguaribe (CE) rivers valleys. The maximum phosphate sorption capacity was highly correlated with the values of remaining P, indicating that it can be used as a measure to estimate the P capacity factor of these soils. Maximum P sorption capacity correlated with Fe2O3 and Ca2+ contents and pH values. These results demonstrate that P sorption is explained by P adsorption on the surface of iron oxides and by its precipitation with Ca2+ in alkaline soils. The contact time increases promote plant P contents decreased substantially in the first 30 to 60 days after fertilization and decreased until 120 days of incubation but then tended to stabilize at the longest soil P contact times.

The clay content and P-remnant estimate the P capacity factor in alkaline soils.In alkaline soils, there is a predominance of P­Ca and P­Fe.The availability of P stabilizes after 120 days.The largest corn biomass occurs between the P doses of 256­288 mg dm⁻³.

Multiple exposure pathways and health risk assessment of potentially harmful elements for children and adults living in a coal region in Brazil.

Energy generated by coal can contaminate the environment by releasing toxic elements, including metals. The human health risk assessment (HHRA) associated with geographic information system (GIS) tools can assist the management of contaminated areas, such as coal mining areas. The objective of the study was to carry out the assessment and spatialization of the risk to human health of potentially hazards elements (PHEs) in the soil for children and adults, from multiple exposure routes (oral, inhalation and dermal) in the Candiota mines, largest coal mining region of Brazil. The non-carcinogenic risks (HQ) of PHEs (Cu, Pb, Zn, Ni, Cr, Fe, Mn, Cd, As and Se) and carcinogenic risks of As were estimated and spatialized. The results revealed a risk for children exposure to Mn, with greatest contribution through dermal route. Mn (HQderm 72.41-96.09% and HQinh 40.84-82.52%) and Fe (HQo 43.90-81.44%) were the metals with greatest contribution to human health risk among studied population. As did not present carinogenic risk to adults. The spatial distribution of non-carcinogenic risk showed that Cr, As, Fe, Pb, Ni, Zn and Cu have higher HInc close to the coal mining areas, while Mn, Se and Cd have the highest HInc values in surrounding municipalities (Pinheiro Machado; Pedras Altas and Hulha Negra). The use of HHRA associated with GIS tools provides important elements for decision-making in the management of contaminated sites, indicating chemical elements, locations, routes of exposure and priority target populations.

Emissions monitoring and carcinogenic risk assessment of PM10-bounded PAHs in the air from Candiota's coal activity area, Brazil.

The city of Candiota contains a great amount of coal resources. Coal activities, including coal combustion, are major releasers of polycyclic aromatic hydrocarbons (PAHs). The PAHs are considered priority air pollutants regarding their large carcinogenic potential. So, the carcinogenic risk assessment of populations living near areas with PAH sources is mandatory. This study aimed to evaluate the carcinogenic health risk of the PAH inhalation exposure of individuals living in Candiota City. A total of 158 individuals were enrolled in the study. Monitoring of PAH and meteorological parameters were carried out, and the health risk assessment was determined through the benzo(a)pyrene equivalent toxic equivalent quotient (BaP-TEQ) and the incremental lifetime cancer risk (ILCR) estimation. The coal activity area of Candiota demonstrated an annual PAH concentration of 27.7 ng/m3, PM10 concentration of 26.3 µg/m3, SO2 concentration of 9.5 µg/m3, a BaP-TEQ value of 0.3 ng/m3, and a daily inhalation of 62.4 ng/day. The comparison among seasons showed no difference in PAH concentration and BaP-TEQ. It was observed ILCR values of 2.8 × 10-6 and 2.6 × 10-6 for estimation based on reference and real values, respectively, and these levels were above the reference limit of 10-6, indicating cancer risk. Therefore, an epidemiological survey of cancer cases in the region and its relationship with environmental exposure and air pollutants levels must be required.

Trends in pneumoconiosis in Brazil, 1979-2019.

BACKGROUND: Pneumoconiosis is a lung disease related to exposure to dust in the workplace. The disease can induce irreversible damage to health, especially in lung tissue, and can cause progressive and permanent physical disabilities. AIMS: This study evaluated the temporal and spatial distribution of mortality rates (1979-2019) and hospital admissions (1995-2019) for pneumoconiosis in Brazil. METHODS: The outcomes were hospitalization and death due to pneumoconiosis: codes 500-506 according to the ICD-9 and J60-J66 according to the ICD-10. Data from this retrospective ecological study were collected from the Brazilian Ministry of Health database. RESULTS: Hospitalization for pneumoconiosis has decreased in all regions of Brazil. Hospitalizations occurred predominantly in men aged over 40 years. Death rates showed a temporal increase in all regions. Deaths occurred predominantly in men aged over 50 years. The highest hospitalization and death rates were in the states of the Midwest and South Regions. CONCLUSIONS: Pneumoconiosis is a preventable occupational disease, and ongoing occurrences of hospitalizations and deaths highlight the importance of inspecting industries and controlling occupational and environmental exposures.

Unexpected reduction in ozone levels in a mid-size city during COVID-19 lockdown.

The current study evaluated ozone levels through passive samplers installed in 4 different points in a medium-sized city (Rio Grande, Brazil) with naturally low NO2 levels during a week of COVID-19 lockdown. Additionally, we evaluated the consequences of this response with regard to human health risk assessment and reduction of hospital admissions and ozone-related deaths. The reduction in ozone levels, one month after the implementation of containment measures, varied between 26 and 64% (average of 44%), in the different studied sites. The reduction of human mobility during the pandemic reduced the levels of ozone in Rio Grande city and consequently will bring benefits to health services in the municipality. This unexpected reduction in O3 levels must be related to the low 'natural' levels of NO2 in the city, which make the contribution of other precursors important for the fluctuation of O3 levels.

Benserazide as a potential novel fetal hemoglobin inducer: an observational study in non-carriers of hemoglobin disorders.

Induction of fetal hemoglobin production with hydroxyurea is an effective strategy in sickle cell disease and beta thalassemias, but up to 20% of patients do not respond to or cannot tolerate it. Benserazide is used in the treatment of Parkinson's disease and was noticed to induce gamma globin in preclinical models. We hypothesized that chronic treatment with benserazide-containing medication may be associated with increase in HbF production and in circulating F-cells. Blood samples were collected from 50 subjects including 35 patients on benserazide for Parkinson's disease, 10 healthy controls, and 5 patients with sickle cell anemia as positive controls for high fetal hemoglobin. We found a strong correlation between HbF and circulating F-cells in the entire population, but we found no significant increase in HbF and F-cell percentage in patients taking benserazide up to 700 mg daily. No hematologic abnormalities attributable to benserazide use after up to 22 years were detected. Our data support long-term safety and tolerability of benserazide at doses ten times higher than used in preclinical models to induce fetal hemoglobin. Further clinical trials enrolling patients with sickle cell disease and thalassemia are warranted to provide insight into its efficacy to treat those populations.

Health risk assessment in urban parks soils contaminated by metals, Rio Grande city (Brazil) case study.

Soils and artificial surfaces of urban parks can be contaminated by toxic substances and offer risk to the human health, especially to children. Rio Grande city, southern Brazil, is a peculiar site from the point of view of environmental contamination, since the current levels of contamination reflect an accumulation of different polluting sources started in the 18th century up to the urban and industrial sources of the present. The history of Hg contamination refers to the use of Hg salts in textile activities in the 18th century and the consequent use of contaminated sediments to land urban areas. The current contamination involves metals such as Cu, Ni, Pb and Zn is related to the high degree of urbanization in the city, as well as the petrochemical and fertilizer industry. The study aimed to achieve a human health risk assessment of urban parks soils, specifically for Cu, Hg, Ni, Pb and Zn. To carry out the risk assessment using the USEPA model, three urban parks with a history of contamination were studied, using different soil exposure pathways (oral, dermal and inhalation) in the carcinogenic (Ni and Pb) and non-carcinogenic (Cu, Hg, Ni, Pb and Zn) scenarios for children and adults. The non-carcinogenic risk of Pb was found in the three urban parks studied, for children and Hg in two urban parks. Pb and Ni showed no carcinogenic risk. Even so, the high non-carcinogenic risk of Hg and Pb showed that the contamination of the past and the present are found in the urban parks of Rio Grande city, putting the health of children who use these collective spaces at risk.

Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population.

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.

Maternal, neonatal and socio-economic factors associated with intellectual development among children from a coal mining region in Brazil.

Coal is the most aggressive energy sources in the environment. Several adverse outcomes on children's health exposure to coal pollutants have been reported. Pollutants from coal power plants adversely affect the intellectual development and capacity. The present study aimed to evaluate the intellectual development and associated factors among children living a city under the direct influence (DI) and six neighboring municipalities under the indirect influence (II) of coal mining activity in the largest coal reserve of Brazil. A structured questionnaire was completed by the child's guardian, and Raven's Progressive Color Matrices were administered to each child to assess intellectual development. A total of 778 children participated. In general, no significant difference was observed between the two cities. The DI city had better socioeconomic conditions than the II municipalities according to family income (< 0.001). The prevalence of children who were intellectually below average or with intellectual disabilities was 22.9%, and there was no significant difference (p > 0.05) between municipalities. In both unadjusted and adjusted analyses, intellectual development was associated with maternal age, marital situation and maternal education level, birth weight, breast feeding, frequent children's daycare, paternal participation in children's care and child growth. Living in the DI area was not associated with intellectual disability. The results suggest that socioeconomic conditions and maternal and neonatal outcomes are more important than environmental factors for intellectual development of children living in a coal mining area.

Selenium dietary intake, urinary excretion, and toxicity symptoms among children from a coal mining area in Brazil.

Selenium (Se) is necessary for several physiological functions in the human body; however, high concentrations of this element in coal mining areas raise the possibility of Se-related health risks. Children are much more vulnerable and at risk to environmental hazards than adults. The largest coal mining area of Brazil is located in the city of Candiota, where previous studies point to significant urinary Se concentrations among children. Food intake is the main Se source. The study aimed to evaluate dietary Se intake, as well as urinary Se excretion and classic symptoms of Se intoxication among children from Candiota and a control city in the same region. A cross-sectional study was carried out, with participation from 242 children between 6 and 12 years old in two cities in Rio Grande do Sul state, Brazil. Socioeconomic variables, dietary intake, and Se toxicity symptoms were evaluated through a structured questionnaire, and urinary Se levels were measured. Children from both cities had normal levels of Se intake and urinary excretion; however, children from Candiota had significantly higher levels of Se in both parameters in relation to the control city, especially for Se urinary excretion. There was low prevalence of Se toxicity symptoms. We conclude that coal mining activities may increase Se intake in children and consequently its urinary excretion.

Human health risk assessment of metals and anions in surface water from a mineral coal region in Brazil.

Coal mining releases high concentration elements to the environment, which can be deposited in surface water, causing several human health problems. Candiota mine in the south of Brazil is the largest coal reserves in the country, representing approximately 40% of total national coal reserves. Therefore, the present study aimed to estimate the chronic daily dose and the non-carcinogenic risk index for metals and anions in surface waters of Candiota Region, using the USEPA protocols for Human Health Risk Assessment. A total of eight water samples were collected over a distance of up to 15 km from the emission sources of the thermal power generation companies, then the Chronic Daily Intake (CDI), Hazard Quotient (HQ), Hazard Index (HI), and sum of Hazard Index (ΣHI) were calculated. All the elements and anions evaluated showed natural concentrations for continental fresh waters according to Brazilian legislation, except Pb. Individually, none of the metals Pb, As, Cd, Ni, and Se or anions F- and NO3- showed an HI value greater than 1. However, the sum of HI (ΣHI) (five metals and two anions) by sample point showed values close to 1, for one of the eight points analyzed. Pb and Fe were the elements that most contribute to the risk values in the sample points of the study area. Although, there is no human health risk in this scenario, this investigation highlight priority elements to future investigations in coal mine areas. In the current region, Pb and F- as priority elements for future studies.

Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats.

Brain death (BD) leads to a systemic inflammation associated with the activation of coagulation, which could be related to decreased microcirculatory perfusion. Evidence shows that females exhibit higher platelet aggregability than males. Thus, we investigated sex differences in platelets, coagulation and microcirculatory compromise after BD. BD was induced in male and female (proestrus) Wistar rats. After 3 h, we evaluated: (i) intravital microscopy to evaluate mesenteric perfusion and leucocyte infiltration; (ii) platelet aggregation assay; (iii) rotational thromboelastometry; and (iv) Serum NOx- . Female rats maintained the mesenteric perfusion, whereas male reduced percentage of perfused vessels. Male BD presented higher platelet aggregation than the controls. In contrast, female BD had lower platelet aggregation than the control. Thromboelastometry indicated a reduction in clot firmness with increased clotting time in the female group compared with the male group. Serum NOx- level in female BD was higher than that in the male BD and female control. There is sex dimorphism in platelet function and clotting process, which are altered in different ways by BD. Thus, it is possible to connect the reduction in microcirculatory perfusion in males to intravascular microthrombi formation and the maintenance of perfusion in females to a higher inflammatory response and NO synthesis.

Treatment with 17ß-estradiol protects donor heart against brain death effects in female rat.

The viability of donor organs is reduced by hemodynamic and immunologic alterations caused by brain death (BD). Female rats show higher heart inflammation associated with the reduction in female sex hormones after BD. This study investigated the effect of 17ß-estradiol (E2) on BD-induced cardiac damage in female rats. Groups of female Wistar rats were assigned: Sham-operation (Sham), brain death (BD), treatment with E2 (50 µg/ml, 2 ml/h) 3 h after BD (E2-T3), or immediately after BD confirmation (E2-T0). White blood cell (WBC) count was analyzed; cytokines and troponin-I were quantified. Heart histopathological changes and expression of endothelial nitric oxide synthase, endothelin-1, intercellular adhesion molecule-1, BCL-2, and caspase-3 were evaluated. Cardiac function was continuously assessed for 6 h by left ventricular pressure-volume loop analysis. E2 decreased the BD-induced median serum concentration of troponin-I (BD:864.2 vs. E2-T0:401.4; P = 0.009), increased BCL-2 (BD:0.086 vs. E2-T0:0.158; P = 0.0278) and eNOS median expression in the cardiac tissue (BD:0.001 vs. E2-T0:0.03 and E2-T3:0.0175; P < 0.0001), and decreased caspase-3 (BD:0.025 vs. E2-T0:0.006 and E2-T3:0.019; P = 0.006), WBC counts, leukocyte infiltration, and hemorrhage. 17ß-estradiol treatment was effective in reducing cardiac tissue damage in brain-dead female rats owing to its ability to reduce leukocyte infiltration and prevent cardiomyocyte apoptosis.

The influence of female sex hormones on lung inflammation after brain death - an experimental study.

Organ donor's age negatively influences graft survival of organs, increasing risk of complications. Aging occurs in both men and women; however, the menopause marks a decrease in sex hormones and a sudden increase in the process of vascular aging. We investigated sex hormones' influence on the lung inflammatory process induced by BD in female rats. Wistar rats were grouped as: female rats from high estradiol to heat period (non-OVx) and ovariectomized (OVx) female rats. Ovariectomy was carried out 10 days before BD. BD was induced using intracranial balloon rapid inflation. Serum hormones and inflammatory mediators were quantified, leukocytes and platelets counted and lung samples were collected for RT-PCR, immunohistochemical, and histological analysis. Female sex hormones and corticosterone were reduced 6 h after BD in non-OVx group. The infiltration of leukocytes in female non-OVx lungs was higher compared to OVx. G-CSF, VEGF, and CINC-1 were found increased in non-OVx group serum in comparison to OVx. Lung mediators were increased in non-OVx rats compared to controls. The acute reduction of sex hormones induced by BD appears to have a worse effect on lung inflammation than a reduction that has happened over a prolonged period of time, allowing a physiological adaptation prior to BD.

The alternative sigma factor SigF is a key player in the control of secretion mechanisms in Synechocystis sp. PCC 6803.

Cyanobacterial alternative sigma factors are crucial players in environmental adaptation processes, which may involve bacterial responses related to maintenance of cell envelope and control of secretion pathways. Here, we show that the Group 3 alternative sigma factor F (SigF) plays a pleiotropic role in Synechocystis sp. PCC 6803 physiology, with a major impact on growth and secretion mechanisms, such as the production of extracellular polysaccharides, vesiculation and protein secretion. Although ΔsigF growth was significantly impaired, the production of released polysaccharides (RPS) increased threefold to fourfold compared with the wild-type. ΔsigF exhibits also impairment in formation of outer-membrane vesicles (OMVs) and pili, as well as several other cell envelope alterations. Similarly, the exoproteome composition of ΔsigF differs from the wild-type both in amount and type of proteins identified. Quantitative proteomics (iTRAQ) and an in silico analysis of SigF binding motifs revealed possible targets/pathways under SigF control. Besides changes in protein levels involved in secretion mechanisms, our results indicated that photosynthesis, central carbon metabolism and protein folding/degradation mechanisms are altered in ΔsigF. Overall, this work provided new evidences about the role of SigF on Synechocystis physiology and associates this regulatory element with classical and non-classical secretion pathways.

Selective α-Synuclein Knockdown in Monoamine Neurons by Intranasal Oligonucleotide Delivery: Potential Therapy for Parkinson's Disease.

Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson's disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration. Here, we used this strategy to conjugate inhibitory oligonucleotides, siRNA and antisense oligonucleotide (ASO), with the triple monoamine reuptake inhibitor indatraline (IND), to selectively reduce α-synuclein expression in the brainstem monoamine nuclei of mice after intranasal delivery. Following internalization of the conjugated oligonucleotides in monoamine neurons, reduced levels of endogenous α-synuclein mRNA and protein were found in substantia nigra pars compacta (SNc), ventral tegmental area (VTA), dorsal raphe nucleus (DR), and locus coeruleus (LC). α-Synuclein knockdown by ∼20%-40% did not cause monoaminergic neurodegeneration and enhanced forebrain dopamine (DA) and 5-HT release. Conversely, a modest human α-synuclein overexpression in DA neurons markedly reduced striatal DA release. These results indicate that α-synuclein negatively regulates monoamine neurotransmission and set the stage for the testing of non-viral inhibitory oligonucleotides as disease-modifying agents in α-synuclein models of PD.