RESUMO
The infralimbic (IL) cortex dysfunction has been implicated in major depressive disorder (MDD), yet the precise cellular and molecular mechanisms remain poorly understood. In this study, we investigated the role of layer V pyramidal neurons in a mouse model of MDD induced by repeated lipopolysaccharide (LPS) administration. Our results demonstrate that three days of systemic LPS administration induced depressive-like behavior and upregulated mRNA levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß (TGF-ß) in the IL cortex. Electrophysiological recordings revealed a significant decrease in the intrinsic excitability of layer V pyramidal neurons in the IL following systemic LPS exposure. Importantly, chemogenetic activation of IL pyramidal neurons ameliorated LPS-induced depressive-like behavior. Additionally, LPS administration significantly increased microglial activity in the IL, as evidenced by a greater number of Ionized calcium binding adaptor molecule-1 (IBA-1)-positive cells. Morphometric analysis further unveiled enlarged soma, decreased branch numbers, and shorter branch lengths of microglial cells in the IL cortex following LPS exposure. Moreover, the activation of pyramidal neurons by clozapine-N-oxide increased the microglia branch length but did not change branch number or cytosolic area. These results collectively suggest that targeted activation of pyramidal neurons in the IL cortex mitigates microglial response and ameliorates depressive-like behaviors induced by systemic LPS administration. Therefore, our findings offer potential therapeutic targets for the development of interventions aimed at alleviating depressive symptoms by modulating IL cortical circuitry and microglial activity.
Assuntos
Lipopolissacarídeos , Microglia , Células Piramidais , Animais , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Camundongos Endogâmicos C57BL , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/tratamento farmacológico , Clozapina/farmacologia , Clozapina/análogos & derivados , Modelos Animais de Doenças , Transtorno Depressivo Maior/metabolismoRESUMO
OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL). METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher's exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (ß2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40â¯g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (ß2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40â¯g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.
Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Adulto , Adulto Jovem , Idoso de 80 Anos ou mais , Prognóstico , Adolescente , Microglobulina beta-2/sangue , Invasividade NeoplásicaRESUMO
Nitrogen narcosis is a neurological syndrome that manifests when humans or animals encounter hyperbaric nitrogen, resulting in a range of motor, emotional, and cognitive abnormalities. The anterior cingulate cortex (ACC) is known for its significant involvement in regulating motivation, cognition, and action. However, its specific contribution to nitrogen narcosis-induced hyperlocomotion and the underlying mechanisms remain poorly understood. Here we report that exposure to hyperbaric nitrogen notably increased the locomotor activity of mice in a pressure-dependent manner. Concurrently, this exposure induced heightened activation among neurons in both the ACC and dorsal medial striatum (DMS). Notably, chemogenetic inhibition of ACC neurons effectively suppressed hyperlocomotion. Conversely, chemogenetic excitation lowered the hyperbaric pressure threshold required to induce hyperlocomotion. Moreover, both chemogenetic inhibition and genetic ablation of activity-dependent neurons within the ACC reduced the hyperlocomotion. Further investigation revealed that ACC neurons project to the DMS, and chemogenetic inhibition of ACC-DMS projections resulted in a reduction in hyperlocomotion. Finally, nitrogen narcosis led to an increase in local field potentials in the theta frequency band and a decrease in the alpha frequency band in both the ACC and DMS. These results collectively suggest that excitatory neurons within the ACC, along with their projections to the DMS, play a pivotal role in regulating the hyperlocomotion induced by exposure to hyperbaric nitrogen.
RESUMO
PURPOSE: The potential relationship between impacted mandibular third molar and lingual bone thickness was investigated by quantitative measurement of lingual bone thickness, and a three-dimensional visualization model of lingual bone was established. METHODS: Image data of 200 cases of mandibular impacted third molar were collected from the database of Hefei Stomatological Hospital. Thickness measurement and three-dimensional reconstruction of lingual bone at different measurement sites were performed by Simplant Pro software. Statistical analysis was performed using SPSS 22.0 software package, and the comparison of lingual thickness at different measurement sites was performed using rank sum test. Whether the thickness of bone plate was "high-risk type" was taken as the result variable, different related factors were analyzed by logistic regression. RESULTS: The lingual bone at the middle point of the root of the third molar was the thinnest. Multiple teeth, mesio-inclined and dial-inclined teeth, and Class â ¡ and â ¢ impacted teeth had thin lingual bone(Pï¼0.05). The mesial and distal inclines were observed, and the lingual bone was thin in the root apical region of the teeth in Class â ¡ and Class â ¢(Pï¼0.05). In the lower impacted teeth, the thin lingual bone at the central crown site was more likely to be found in Class â ¢ teeth(Pï¼0.05). CONCLUSIONS: The thickness of lingual bone was related to the number of impacted tooth roots, tilt direction and impacted type. In the extraction of impacted teeth, the above factors should be considered, and the injury of lingual nerve, lingual bone and surrounding soft tissue should be vigilant.