RESUMEN
Hyperfunction of the dopamine system has been implicated in manic episodes in bipolar disorders. How dopaminergic neuronal function is regulated in the pathogenesis of mania remains unclear. Histaminergic neurons project dense efferents into the midbrain dopaminergic nuclei. Here, we present mice lacking dopaminergic histamine H2 receptor (H2R) in the ventral tegmental area (VTA) that exhibit a behavioral phenotype mirroring some of the symptoms of mania, including increased locomotor activity and reduced anxiety- and depression-like behavior. These behavioral deficits can be reversed by the mood stabilizers lithium and valproate. H2R deletion in dopaminergic neurons significantly enhances neuronal activity, concurrent with a decrease in the γ-aminobutyric acid (GABA) type A receptor (GABAAR) membrane presence and inhibitory transmission. Conversely, either overexpression of H2R in VTA dopaminergic neurons or treatment of H2R agonist amthamine within the VTA counteracts amphetamine-induced hyperactivity. Together, our results demonstrate the engagement of H2R in reducing VTA dopaminergic activity, shedding light on the role of H2R as a potential target for mania therapy.
RESUMEN
BACKGROUND: Postmenopausal women face a heightened risk of developing new vertebral compression fractures (NVCFs) following percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). This study aimed to develop and validate a visual nomogram model capable of accurately predicting NVCF occurrence post-PKP to optimize treatment strategies and minimize occurrence. METHODS: This retrospective study included postmenopausal women diagnosed with OVCF who underwent PKP at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2016 and January 2021. Patient data, including basic information, surgical details, imaging records, and laboratory findings, were collected. The patients were categorized into two groups based on NVCF occurrence within 2 years post-PKP: the NVCF group and the non-NVCF group. Following the utilization of least absolute shrinkage and selection operator (LASSO) regression for feature selection, a nomogram was constructed. Model differentiation, calibration, and clinical applicability were evaluated using receiver operating characteristic (ROC), calibration, and decision (DCA) curve analyses. RESULTS: In total, 357 patients were included in the study. LASSO regression analysis indicated that cement leakage, poor cement diffusion, and endplate fracture were independent predictors of NVCF. The nomogram demonstrated excellent predictive accuracy and clinical applicability. CONCLUSIONS: This study used LASSO regression to identify three independent predictors of NVCF and developed a predictive model that could effectively predict NVCF occurrence in postmenopausal women. This simple prediction model can support medical decision-making and is feasible for clinical practice.