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2.
Tokai J Exp Clin Med ; 45(2): 75-80, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32602105

RESUMO

CASE PRESENTATION: The patient was a 72-year-old man who consulted with his previous physician for chief complaints of palpitations, fatigue, and blackish feces persisting for 1 month. After confirming the presence of anemia, the patient was referred to our hospital. Blood test findings upon hospital arrival revealed a hemoglobin (Hb) level of 6.0 g/dL. Computed tomography revealed a tumor of 32 mm × 30 mm with a low-density area extending from the bulb to the second part of the duodenum. Magnetic resonance imaging revealed high signal intensity on T1- and T2-weighted imaging and low signal intensity on fat-suppressed T2-weighted imaging, findings consistent with lipoma. Upper gastrointestinal endoscopy revealed a yellowish submucosal tumor that had perforated into the intestinal tract from the external wall extending from the upper corner to the second part of the duodenum. After determining that the tumor was sessile, laparoscopic partial duodenectomy with Roux-en-Y reconstruction was planned and performed. Pathology revealed a yellowish tumor 4 cm × 4 cm in size extending from the pyloric area to the duodenal bulb arising from the tunica muscularis. The present case report details our experience involving a patient who underwent surgical resection for hemorrhagic duodenal lipoma.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Duodenopatias/cirurgia , Neoplasias Duodenais/cirurgia , Duodeno/cirurgia , Hemorragia Gastrointestinal/cirurgia , Laparoscopia/métodos , Lipoma/cirurgia , Idoso , Anastomose em-Y de Roux , Imagem de Difusão por Ressonância Magnética , Duodenopatias/patologia , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/patologia , Duodeno/patologia , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/patologia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/patologia , Masculino
4.
N Engl J Med ; 383(4): 321-333, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32706533

RESUMO

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED. CONCLUSIONS: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).


Assuntos
Duodeno/microbiologia , Microbioma Gastrointestinal , Transtornos do Crescimento/microbiologia , Transtornos da Nutrição do Lactente/complicações , Animais , Bactérias/isolamento & purificação , Bangladesh , Duodenoscopia , Duodeno/patologia , Doença Ambiental/complicações , Fezes/microbiologia , Feminino , Vida Livre de Germes , Crescimento , Transtornos do Crescimento/etiologia , Humanos , Lactente , Doenças Inflamatórias Intestinais/complicações , Fator de Crescimento Insulin-Like I/análise , Enteropatias/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise Multivariada , Proteínas Associadas a Pancreatite/análise , Proteoma/análise
5.
PLoS One ; 15(6): e0234076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520965

RESUMO

This study investigated the effects of oral administration of ß-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of ß-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between ß-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of ß-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with ß-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by ß-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of ß-glucan was significantly upregulated and enhanced the immune response. ß-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 ß-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of ß-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , beta-Glucanas/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Administração Oral , Animais , Duodeno/metabolismo , Duodeno/patologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ocludina/genética , Ocludina/metabolismo , Coelhos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Am J Med Sci ; 360(3): 293-299, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32563569

RESUMO

Hyposplenism is associated with autoimmune diseases, inflammatory bowel disease, severe celiac disease, autoimmune thyroiditis, untreated HIV infection and chronic graft-versus-host disease. The aim of this study was to review the existing data on hyposplenism associated with celiac disease and Hashimoto's autoimmune thyroiditis. Our research was based on a clinical case concerning a 41-year-old female who presented with asthenia, fatigue, dyspepsia and chronic diarrhea. The medical history revealed autoimmune Hashimoto's thyroiditis, type 2 diabetes, fatty liver disease, chronic gastritis and thrombocytosis. Multiple investigations showed hyposplenism and complex autoimmune dysfunction with positive serum markers for celiac disease and type 1 autoimmune hepatitis along with minor symptomatology. The intestinal symptomatology of celiac disease is often hid by hypothyroidism-associated autoimmune thyroiditis. Asymptomatic or minimally symptomatic celiac disease associated with Hashimoto's autoimmune thyroiditis is diagnosed by biomarkers. Hyposplenism in celiac disease can occur regardless of the disease stage, latent or symptomatic.


Assuntos
Doença Celíaca/complicações , Doença de Hashimoto/complicações , Hepatite Autoimune/complicações , Baço/patologia , Adulto , Biópsia , Doença Celíaca/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Duodeno/patologia , Fígado Gorduroso/complicações , Feminino , Gastrite/complicações , Doença de Hashimoto/patologia , Hepatite Autoimune/patologia , Humanos , Imagem por Ressonância Magnética , Trombocitose/complicações
9.
Virchows Arch ; 477(4): 507-515, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32405928

RESUMO

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.


Assuntos
Doença Celíaca/patologia , Duodeno/patologia , Mucosa Intestinal/patologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biópsia , Complexo CD3/análise , Doença Celíaca/imunologia , Criança , Pré-Escolar , Duodeno/imunologia , Feminino , Humanos , Mucosa Intestinal/imunologia , Linfócitos Intraepiteliais/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
10.
Arq Gastroenterol ; 57(1): 74-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294739

RESUMO

BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.


Assuntos
Duodeno/patologia , Dispepsia/microbiologia , Eosinofilia/patologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Adulto , Biópsia , Estudos de Casos e Controles , Duodeno/microbiologia , Dispepsia/patologia , Feminino , Mucosa Gástrica/microbiologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Medicine (Baltimore) ; 99(16): e19888, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312016

RESUMO

RATIONALE: Although percutaneous endoscopic gastrojejunostomy (PEG-J) tubes are believed to reduce the side effect of aspiration, cautious catheter management is required. Intussusception is a serious complication of these tubes. PATIENT CONCERNS: A 7-year-old boy bedridden with hypoxic encephalopathy owing to drowning at the age of 1 year was admitted our hospital with urinary retention for 1 month. At the age of 4 years, a PEG-J tube was inserted. Concomitant with hyperaldosteronemia, an intestinal intussusception from the duodenum to the jejunum was observed via computed tomography (CT). The patient's condition worsened dramatically; gastrointestinal perforation was suspected, and laparotomy was performed. DIAGNOSIS: Jejuno-jejunal intussusception. INTERVENTIONS: Open surgery was performed to release the intussusception. By assessing the reduced intestinal tract, the intussusception starting from a 50 cm portion from the Treitz ligament had been extended to 100 cm from the Treitz ligament. The oral side jejunum was dilated. No evidence of intestinal perforation or strangulated ileus was observed, and the intussusception was manually remediable. OUTCOMES: Preoperative CT examination showed intussusception from the duodenum to the jejunum. Laparotomy showed intussusception on the anal side of the Treitz ligament. With regard to the CT findings associated with the progression of intussusception to the duodenal site, as a result of the telescope phenomenon extending to the duodenum due to the relaxation of the Treitz ligament through repeated intussusception, it was considered that CT examination revealed intussusception extending from the jejunum to the duodenum of oral side. After 3 postoperative weeks, the patient was finally able to return home. LESSONS: If the ileus is observed during the insertion of a PEG-J, clinicians should consider the possibility of intussusception even in the duodenum.


Assuntos
Endoscopia Gastrointestinal/métodos , Derivação Gástrica/efeitos adversos , Intussuscepção/etiologia , Jejunostomia/efeitos adversos , Estômago/cirurgia , Criança , Duodeno/patologia , Duodeno/cirurgia , Derivação Gástrica/instrumentação , Humanos , Doença Iatrogênica , Íleus/diagnóstico , Íleus/etiologia , Intussuscepção/patologia , Doenças do Jejuno/diagnóstico por imagem , Doenças do Jejuno/etiologia , Doenças do Jejuno/patologia , Jejuno/patologia , Jejuno/cirurgia , Laparotomia/métodos , Masculino , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
J Surg Res ; 252: 116-124, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278965

RESUMO

BACKGROUND: Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS: Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS: Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS: Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Duodenais/mortalidade , Neoplasias do Íleo/mortalidade , Neoplasias do Jejuno/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia Adjuvante , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Duodeno/patologia , Duodeno/cirurgia , Feminino , Humanos , Neoplasias do Íleo/patologia , Neoplasias do Íleo/terapia , Íleo/patologia , Íleo/cirurgia , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/terapia , Jejuno/patologia , Jejuno/cirurgia , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
13.
Mol Biol (Mosk) ; 54(1): 146-152, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32163398

RESUMO

Migration of cancer cells from the primary tumor site to nearby tissues is the starting point of the metastatic process. The invasive properties of cells are especially important for carcinomas, since tumor cells need to overcome the basement membrane and go beyond its boundaries to the underlying tissues. Substances that reduce the invasive ability of malignant cells are promising as antimetastatic agents. In the present work, the possibility of inhibiting the ability of different cancer cell lines to migrate under the influence of the Bacillus pumilus ribonuclease (binase) was analyzed using the scratch-wound assay. It was established that binase at non-toxic concentrations (10 µg/mL) reliably suppressed the migratory ability of HuTu 80 human duodenum adenocarcinoma cells incubated with RNase for 48-72 h. The antimetastatic potential of binase is confirmed by molecular modeling data demonstrating the ability of binase to inhibit cellular metalloproteinases that determine the migration of tumor cells.


Assuntos
Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Movimento Celular/efeitos dos fármacos , Duodeno/patologia , Ribonucleases/metabolismo , Ribonucleases/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Metaloproteases/antagonistas & inibidores , Metaloproteases/metabolismo
14.
Ann Hematol ; 99(5): 1121-1128, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32130472

RESUMO

AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.


Assuntos
Duodenopatias/patologia , Duodeno/patologia , Endoscopia Gastrointestinal , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Doenças do Íleo/patologia , Íleo/patologia , Mucosa Intestinal/patologia , Adolescente , Adulto , Idoso , Aloenxertos , Atrofia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
PLoS One ; 15(3): e0230113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142547

RESUMO

BACKGROUND: The drawback of the delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG) is the presence of intraoperative duodenal injury and postoperative anastomotic stenosis, which can occur due to a relatively short duodenal bulb diameter. MATERIALS AND METHODS: From June 2013 to June 2019, 35 patients with gastric cancer underwent TLDG with a modified DSG consisting of linear stapling and single-layer hand suturing in our institution. All anastomotic procedures were performed by the right hand of the operator positioned between the patient's legs. Linear stapling of the posterior walls of the remnant stomach and duodenum without creating a gap was performed using a 45-mm linear stapler, considering the prevention of intraoperative duodenal injury. The stapler entry hole was closed using a single-layer full-thickness hand suturing technique with knotted sutures and a knotless barbed suture. We described the clinical data and outcomes in the present retrospective patient series. RESULTS: No intraoperative duodenal injury occurred in any of the 35 patients. The median staple length at linear stapling of the posterior walls of the remnant stomach and duodenum was 41.7 ± 4.2 (30-45) mm, and 2 patients (5.7%) had a staple length of 30 mm. There were no incidences of postoperative anastomotic stenosis. CONCLUSIONS: We suggest that a modified DSG consisting of linear stapling and single-layer hand suturing performed by an operator positioned between the patient's legs can be one option for B-Ⅰ reconstruction following TLDG because it can aid in preventing both intraoperative duodenal injury and postoperative anastomotic stenosis.


Assuntos
Constrição Patológica/prevenção & controle , Duodeno/lesões , Gastrectomia/métodos , Gastroenterostomia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Duodeno/patologia , Feminino , Coto Gástrico/patologia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Grampeadores Cirúrgicos , Técnicas de Sutura/instrumentação
18.
Nat Neurosci ; 23(3): 327-336, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066981

RESUMO

Parkinson's disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson's disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology.


Assuntos
Encéfalo/patologia , Doenças do Sistema Digestório/patologia , Sinucleinopatias/metabolismo , Sinucleinopatias/patologia , Animais , Duodeno/patologia , Sistema Nervoso Entérico/patologia , Glucosilceramidase/biossíntese , Glucosilceramidase/genética , Mesencéfalo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/patologia , Fibras Nervosas/patologia , Nociceptividade , Gânglio Nodoso/patologia
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