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BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) have been developed recently, in addition to conventional methods, but adverse events of each method have not been fully clarified. We compared outcomes of each method for the appropriate choice. PATIENTS AND METHODS: Patients who underwent CSP, endoscopic mucosal resection (EMR)/hot snare polypectomy (HSP) or UEMR for small and intermediate-sized colorectal polyps between April 2017 and June 2020 were retrospectively examined. The rate of adverse events and recurrences due to each method were determined as main outcomes. Clinical factors related with adverse events were examined. RESULTS: A total of 1,025 patients with 3,163 polyps underwent polypectomy using any of the methods. CSP, EMR/HSP and UEMR were performed for 704 (22.2%), 2,145 (67.8%) and 314 polyps (9.9%), and median size for each method was 4, 6 and 7 mm, respectively. Delayed bleeding for CSP, EMR/HSP and UEMR was 0%, 0.2% and 0.6% (P = 0.15), and perforation was 0%, 0.1% and 0%, respectively (P = 0.62). Recurrence after CSP, EMR/HSP and UEMR was 0.1%, 0.04% and 1.0%, respectively (P < 0.01). Recurrence for UEMR was significantly higher in the early stage of procedure introduction (P = 0.001). Oral anticoagulants were the risk factor for delayed bleeding (P < 0.01, respectively). CONCLUSIONS: There was no significant difference regarding adverse events among each method for small and intermediate-sized polyps, although recurrence rate after UEMR was higher than other methods.
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This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia , Estudos Retrospectivos , Mucosa Intestinal/química , Mucosa Intestinal/diagnóstico por imagem , Ultrassonografia , Índice de Gravidade de Doença , Inflamação , BiomarcadoresRESUMO
Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels and this adaptive myelination is associated with improved learning of motor tasks, suggesting such plasticity may enhance effective learning. In this study, we examined whether another aspect of myelin plasticity-changes in myelin lipid synthesis and composition-may also be associated with motor learning. We combined a motor learning task in mice with in vivo two-photon imaging of neural activity in the primary motor cortex (M1) to distinguish early and late stages of learning and then probed levels of some key myelin lipids using mass spectrometry analysis. Sphingomyelin levels were elevated in the early stage of motor learning while galactosylceramide levels were elevated in the middle and late stages of motor learning, and these changes were correlated across individual mice with both learning performance and neural activity changes. Targeted inhibition of oligodendrocyte-specific galactosyltransferase expression, the enzyme that synthesizes myelin galactosylceramide, impaired motor learning. Our results suggest regulation of myelin lipid composition could be a novel facet of myelin adaptations associated with learning.
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Galactosilceramidas , Bainha de Mielina , Camundongos , Animais , Bainha de Mielina/metabolismo , Galactosilceramidas/metabolismo , Axônios/metabolismo , Neurônios/metabolismo , Oligodendroglia/fisiologiaRESUMO
BACKGROUND: Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. METHODS: We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as "neoplasia," "negative for neoplasia," or "indefinite for neoplasia," and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. RESULTS: Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen's kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837-0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. CONCLUSIONS: Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD.
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Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Ressecção Endoscópica de Mucosa/métodos , Secções Congeladas , Estudos Prospectivos , Gastroscopia , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Biópsia/métodos , Estudos RetrospectivosRESUMO
α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson's disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. To characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3-αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Because this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3-αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson's disease.
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Amiloide/antagonistas & inibidores , Proteína 3 Ligante de Ácido Graxo/metabolismo , Neuroblastoma/patologia , Fragmentos de Peptídeos/farmacologia , Agregação Patológica de Proteínas/prevenção & controle , alfa-Sinucleína/metabolismo , Amiloide/metabolismo , Animais , Proteína 3 Ligante de Ácido Graxo/genética , Humanos , Camundongos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Células Tumorais Cultivadas , alfa-Sinucleína/antagonistas & inibidores , alfa-Sinucleína/genéticaRESUMO
BACKGROUND: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin. METHODS: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission. RESULTS: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023). CONCLUSIONS: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC. TRIAL REGISTRATION: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020.
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Anticorpos Anticitoplasma de Neutrófilos , Colite Ulcerativa , Biomarcadores , Colite Ulcerativa/tratamento farmacológico , Humanos , Mieloblastina , Estudos RetrospectivosRESUMO
BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is an invasive surgical procedure for the knee. Quadruple nerve blocks including continuous femoral nerve block and single-injection sciatic, obturator, and lateral femoral cutaneous nerve blocks can provide effective intraoperative anesthesia and analgesia in the early postoperative period. However, severe pain often appears after the effect of single-injection nerve blocks resolves and that is why we conducted two studies. The first study was to determine whether dexamethasone administered along with local anesthetic for sciatic nerve block could prolong the duration of analgesia in patients given quadruple nerve blocks, including continuous femoral nerve block, for ACL reconstruction using a hamstring tendon autograft. The second study was designed to evaluate any difference in effects from dexamethasone administered perineurally versus intravenously. METHODS: Patients undergoing unilateral arthroscopic ACL reconstruction using a hamstring tendon autograft were enrolled into two studies. The first study was prospectively conducted to see if dexamethasone 4 mg could prolong the duration of analgesia when administered perineurally to the subgluteal sciatic nerve with 0.5% ropivacaine. In the second study, we retrospectively evaluated the effects of intravenous dexamethasone 4 mg as compared with those of perineural dexamethasone to the sciatic nerve block and effects with no dexamethasone. RESULTS: In the first study, perineural dexamethasone prolonged the duration of analgesia by 9.5 h (median duration: 22.5 and 13.0 h with and without perineural dexamethasone, respectively, P = 0.011). In the second study, the duration of analgesia was similarly prolonged for intravenous and perineural dexamethasone compared with no dexamethasone. CONCLUSION: Perineural dexamethasone administered along with local anesthetic for single sciatic nerve block prolonged the duration of analgesia of quadruple nerve blocks for ACL reconstruction, however the effects were not different from those of intravenous dexamethasone. TRIAL REGISTRATION: The protocols of both studies were approved by the Institutional Review Board of Shimane University Hospital, Japan (study number 2821 and 3390 for study 1 and study 2, respectively). Study 1 was registered in University Hospital Medical Information Network Clinical Trials Registry ( UMIN000028930 ). Study 2, which was a retrospective study, was not registered.
Assuntos
Reconstrução do Ligamento Cruzado Anterior , Dexametasona/administração & dosagem , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Ropivacaina/administração & dosagem , Adulto , Anestésicos Locais/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Artroscopia , Feminino , Humanos , Injeções , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Nervo IsquiáticoRESUMO
BACKGROUND: Continuous interscalene brachial plexus block (CISB) provides analgesia after shoulder surgery. However, even a catheter securely fixed at the insertion site may be susceptible to migration, precluding the block from working consistently. We examined to see if catheter tip migration would occur with no catheter-at-skin change after anterior and posterior approaches to CISB in patients undergoing shoulder surgery, and compared the incidence rate and pain scores between approaches and between catheters with and without tip migration, respectively. METHODS: Patients were randomly assigned to receive CISB using either anterior or posterior approach. Catheter tip was observed using a cross-sectional view. The rates of catheter tip migration with no catheter-at-skin change at 24 h after the two approaches were calculated and compared, and pain scores were compared between catheters with and without tip migration after each approach. RESULTS: Fifty-four patients were analyzed. Catheter tip migration occurred at 24 h at a similar rate after both approaches (anterior approach 40.7% versus posterior approach 33.3%, p = 0.78). Worst pain score was significantly higher for 24 h in patients whose catheter tip had migrated as compared with those whose catheter had not migrated after anterior (median [IQR] 53 [42-73] versus 18 [0-50], p = 0.003) and posterior approaches (median [IQR] 63 [57-81] versus 29 [3-47], p < 0.0001). CONCLUSION: In patients undergoing shoulder surgery, an interscalene catheter tip can migrate after both anterior and posterior approaches at a similar rate, even if the catheter insertion length is not changed. The tip migration does decrease the analgesic effect of CISB.
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Anestésicos Locais , Dor Pós-Operatória , Catéteres/efeitos adversos , Estudos Transversais , Humanos , Incidência , Dor Pós-Operatória/epidemiologia , Ombro/cirurgia , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Quadratus lumborum block (QLB) has recently attracted attention as a part of multimodal analgesia after abdominal surgery. It has been shown that programmed intermittent boluses of local anesthetic can produce better analgesia and wider sensory blockade compared with continuous basal infusion with some peripheral nerve blocks. The present study was conducted to see if this theory holds true for QLB in patients undergoing laparoscopic colorectal surgery. METHODS: Fifty patients undergoing laparoscopic colorectal surgery were divided into 2 groups to receive continuous basal infusion (group C) or programmed intermittent boluses (group PIB) of local anesthetic. After surgery, patients received the posterior approach to QLB and a catheter was introduced bilaterally. Patients in group C received a continuous infusion of 0.15% levobupivacaine at 3 ml/h, and those in group PIB received a bolus of 12 ml every 4 h. All patients received intravenous patient-controlled analgesia using fentanyl. Measurements were taken for cumulative fentanyl consumption, pain scores, cutaneous sensory blockade, analgesic requirements, and adverse events for 46 h. RESULTS: The primary outcome of cumulative fentanyl consumption at 22 h showed no significant difference between the groups [group C: 11.9 (11.2-15.5) µg/kg (median (interquartile range)) and group PIB: 12.3 (11.6-15.3), p = 0.473]. Pain scores, demands for rescue analgesics, and spread of cutaneous sensory blockade were similar for the two groups. CONCLUSION: Programmed intermittent boluses of local anesthetic for continuous QLB did not produce better analgesia or wider sensory blockade compared with continuous basal infusion in patients undergoing laparoscopic colorectal surgery.
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Cirurgia Colorretal , Laparoscopia , Bloqueio Nervoso , Anestésicos Locais , Método Duplo-Cego , Humanos , Bloqueio Nervoso/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controleRESUMO
BACKGROUND: Continuous femoral nerve block (FNB) has been effectively used after total hip arthroplasty (THA). Recently the anterior approach to quadratus lumborum block (QLB) has been shown to produce postoperative pain relief after THA. Continuous QLB would benefit from a catheter insertion site that is farther away from the surgical site compared with continuous FNB. In this randomized controlled study, we compared analgesic effects of the two techniques in patients undergoing THA. METHODS: Thirty patients undergoing THA were randomly allocated into two groups receiving continuous QLB and FNB. Under ultrasound guidance, QLB and FNB were conducted before general anesthesia using 0.25% levobupivacaine 30 ml and 0.5% levobupivacaine 15 ml, respectively, and a catheter was introduced. Postoperatively, all patients received continuous infusion of 0.125% levobupivacaine at 4 ml/h. Postoperative measurements included visual analog scale (VAS) pain scores at rest and on movement, postoperative analgesic demands, cutaneous sensory blockade and adverse events for 48 h. RESULTS: Six patients were excluded and 24 patients (13 and 11 patients in QLB group and FNB, respectively) were analyzed. VAS scores on movement at 6 h [median (IQR): 67 (41-80) and 38 (22-41) in QLB and FNB groups, respectively, p = 0.008] and 24 h [60 (40-80) and 39 (28-64) in QLB and FNB groups, respectively, p = 0.018] were lower with FNB than with QLB. QLB did not produce consistent cutaneous sensory blockade. CONCLUSIONS: Analgesic effects of continuous QLB were inferior to those of continuous FNB in patients undergoing THA under the current study condition.
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Anestesia por Condução , Artroplastia de Quadril , Bloqueio Nervoso , Anestésicos Locais , Nervo Femoral , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controleRESUMO
A ring-shaped ulcer was observed in the ileum of a 70-year-old male patient with capsule endoscopy of the small intestine performed for detailed investigation of black stools and iron deficiency anemia. Non-steroidal anti-inflammatory drugs (NSAIDs) use in patch form was considered as the etiology. The NSAIDs patches were discontinued, and protective therapy for small intestinal mucosa was initiated. The anemia improved;however, ileus originating from the site of the ulcer required surgical resection. The resected specimen showed no specific pathological findings. Based on the clinical findings, the patient was diagnosed with NSAIDs-induced small intestinal ulcer. The use of NSAIDs patches should be considered as a potential cause of injury to gastrointestinal mucosa.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Endoscopia por Cápsula , Enteropatias/induzido quimicamente , Idoso , Humanos , Enteropatias/diagnóstico , Mucosa Intestinal , Intestino Delgado , Masculino , ÚlceraRESUMO
A 74-year-old male who was receiving endocrine therapy for prostate cancer, with multiple bone and lymph node metastases (T2bN1M1 Stage D2), underwent follow-up computed tomography (CT). The CT revealed multiple liver metastases, a high serum CEA level, and an unchanged PSA level. Upper gastrointestinal endoscopy showed an elevated lesion with mucosal erosion on the lesser curvature of the middle gastric corpus, revealed to be a metastatic prostate cancer lesion following immunohistochemical confirmation. This case demonstrates the potential for gastric metastases in patients with advanced prostate cancer and high serum CEA levels.
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Neoplasias Hepáticas/secundário , Neoplasias da Próstata/diagnóstico , Neoplasias Gástricas/secundário , Idoso , Antígeno Carcinoembrionário , Humanos , Neoplasias Hepáticas/diagnóstico , Metástase Linfática , Masculino , Neoplasias da Próstata/patologia , Neoplasias Gástricas/diagnósticoRESUMO
Accumulating evidence suggests that dysregulation of histone modification is involved in the pathogenesis and/or pathophysiology of psychiatric disorders. However, the abnormalities in histone modification in the animal model of schizophrenia and the efficacy of antipsychotics for such abnormalities remain unclear. Here, we investigated the involvement of histone modification in phencyclidine-induced behavioral abnormalities and the effects of antipsychotics on these abnormalities. After repeated phencyclidine (10 mg/kg) treatment for 14 consecutive days, mice were treated with antipsychotics (clozapine or haloperidol) or the histone deacetylase inhibitor sodium butyrate for 7 d. Repeated phencyclidine treatments induced memory impairment and social deficit in the mice. The acetylation of histone H3 at lysine 9 residues decreased in the prefrontal cortex with phencyclidine treatment, whereas the expression level of histone deacetylase 5 increased. In addition, the phosphorylation of Ca²âº/calmodulin-dependent protein kinase II in the nucleus decreased in the prefrontal cortex of phencyclidine-treated mice. These behavioral and epigenetic changes in phencyclidine-treated mice were attenuated by clozapine and sodium butyrate but not by haloperidol. The dopamine D1 receptor antagonist SCH-23390 blocked the ameliorating effects of clozapine but not of sodium butyrate. Furthermore, clozapine and sodium butyrate attenuated the decrease in expression level of GABAergic system-related genes in the prefrontal cortex of phencyclidine-treated mice. These findings suggest that the antipsychotic effect of clozapine develops, at least in part, through epigenetic modification by activation of the dopamine D1 receptor in the prefrontal cortex.
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Antipsicóticos/farmacologia , Clozapina/farmacologia , Epigênese Genética/efeitos dos fármacos , Abuso de Fenciclidina/tratamento farmacológico , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Animais , Benzazepinas/farmacologia , Ácido Butírico/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Antagonistas de Dopamina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Alucinógenos/farmacologia , Haloperidol/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Histona Desacetilases/metabolismo , Histonas/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Fenciclidina/farmacologia , Abuso de Fenciclidina/complicações , Abuso de Fenciclidina/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
Wheelchair cushions are recommended to be used with wheelchair and can protect the buttocks from pain and injury by relieving interface pressure for wheelchair users. However, further investigations are required for proper use in response to the development of new types of wheelchair cushions. The objective of this study was to evaluate physical characteristics of wheelchair cushions by comparing pressure redistributing effects of four types of cushions. The participants were 16 healthy adults who consented to participate in this study. A pressure mapping system (CONFORMat, Nitta Corp.) was used for the measurements. Pressure at ischium was measured immediately after the stabilization of the sitting posture and 10 minutes after. The pressure at ischium significantly decreased with any wheelchair cushions (P < 0.01). A significant negative correlation between body mass index and pressure at ischium was observed without a wheelchair cushion (r = - 0.70), however, the correlation disappeared upon use of a wheelchair cushion. The pressure at ischium increased over time with cushions of urethane, air, and urethane-air hybrid while that with the 3D thermoplastic elastomer cushion did not, and the change in the pressure was statistically less than that in other cushions (P < 0.01). Use of wheelchair cushions was effective in redistribution of the pressure at ischium, and the overtime change in the pressure depends on the type of used cushions.
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Elastômeros , Desenho de Equipamento , Ísquio , Pressão , Cadeiras de Rodas , Humanos , Adulto , Elastômeros/química , Masculino , Feminino , Uretana/química , Adulto Jovem , Índice de Massa Corporal , Úlcera por Pressão/prevenção & controleRESUMO
It has been reported that repeated phencyclidine (PCP) treatment induces schizophrenia-like behavior in mice. L-Tryptophan (Trp) concentrations in brain tissues of control (n = 8) and PCP-treated mice (10 mg/kg/day, s.c., 14 days, n = 10) were determined using high-performance liquid chromatography (HPLC) with fluorescence detection. The HPLC method involved pre-column fluorescence derivatization with (R)-(-)-4-(N,N-dimethylaminosulfonyl)-7-(3-isothiocyanatopyrrolidin-1-yl)-2,1,3-benzoxadiazole (DBD-PyNCS). Eight different parts of the brain, namely, the frontal cortex, nucleus accumbens, striatum, hippocampus, amygdala, thalamus, hypothalamus, and cerebellum, of both groups were investigated. A significant decrease in the L-Trp concentration in the nucleus accumbens (p = 0.024) and hippocampus (p = 0.027) was observed in PCP-treated mice, suggesting that alteration of the L-Trp metabolism might occur in these brain parts.
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Encéfalo/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fenciclidina/farmacologia , Triptofano/metabolismo , Animais , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Isotiocianatos , Masculino , Camundongos , Oxidiazóis , Fenciclidina/efeitos adversos , Esquizofrenia/induzido quimicamente , Triptofano/análiseRESUMO
Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage.
Assuntos
Microglia , Córtex Visual , Animais , Neurônios/fisiologia , Sinapses/fisiologia , Células Piramidais , Córtex Visual/fisiologia , Plasticidade Neuronal/fisiologia , Vibrissas/fisiologia , Córtex Somatossensorial/fisiologiaRESUMO
Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.
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Meio Ambiente , Histona Desacetilases/metabolismo , Fenciclidina/toxicidade , Agitação Psicomotora/enzimologia , Agitação Psicomotora/prevenção & controle , Comportamento Social , Fatores Etários , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Agitação Psicomotora/psicologiaRESUMO
Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.
Assuntos
Neuralgia , Córtex Somatossensorial , Humanos , Hiperalgesia/metabolismo , Neuralgia/etiologia , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Córtex Somatossensorial/metabolismo , Medula EspinalRESUMO
We aimed to develop a brief, preclinical test to screen the reduced hippocampal volume that is a marker of early dementia [Cognitive Quotient (CQ) test]. We performed an observational study of adult subjects who underwent brain MRI in seven institutions from February 2018 to May 2019. The CQ test consists of five components: (1) digits forward, (2) digits backward, (3) Stroop test, (4) simple calculation, and (5) mental rotation. The primary outcome measure was hippocampal volume. We separated the data into derivation (n = 322) and validation cohorts (n = 96). In the derivation cohort, we built two scoring systems using the results of CQ test (model 1 and 2). In the validation cohort, we validated the correlation of the scoring systems with hippocampal volume. In the derivation cohort, there was a moderate correlation between the scoring systems and hippocampal volume [e.g., correlation coefficient = 0.62 in model 1 (95% CI 0.44-0.75)]. Likewise, in the validation cohort, there was a moderate correlation between the scoring systems and hippocampal volume [e.g., correlation coefficient = 0.54 in model 2 (95% CI 0.38-0.67)]. In this analysis of 418 participants, the score of newly developed CQ test was correlated with hippocampal volume.