Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Semin Cell Dev Biol ; 144: 67-76, 2023 07 30.
Article in English | MEDLINE | ID: mdl-36115764

ABSTRACT

The use of antidepressants during pregnancy benefits the mother's well-being, but the effects of such substances on neurodevelopment remain poorly understood. Moreover, the consequences of early exposure to antidepressants may not be immediately apparent at birth. In utero exposure to selective serotonin reuptake inhibitors (SSRIs) has been related to developmental abnormalities, including a reduced white matter volume. Several reports have observed an increased incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) after prenatal exposure to SSRIs such as sertraline, the most widely prescribed SSRI. The advent of human-induced pluripotent stem cell (hiPSC) methods and assays now offers appropriate tools to test the consequences of such compounds for neurodevelopment in vitro. In particular, hiPSCs can be used to generate cerebral organoids - self-organized structures that recapitulate the morphology and complex physiology of the developing human brain, overcoming the limitations found in 2D cell culture and experimental animal models for testing drug efficacy and side effects. For example, single-cell RNA sequencing (scRNA-seq) and electrophysiological measurements on organoids can be used to evaluate the impact of antidepressants on the transcriptome and neuronal activity signatures in developing neurons. While the analysis of large-scale transcriptomic data depends on dimensionality reduction methods, electrophysiological recordings rely on temporal data series to discriminate statistical characteristics of neuronal activity, allowing for the rigorous analysis of the effects of antidepressants and other molecules that affect the developing nervous system, especially when applied in combination with relevant human cellular models such as brain organoids.


Subject(s)
Autism Spectrum Disorder , Selective Serotonin Reuptake Inhibitors , Pregnancy , Female , Infant, Newborn , Animals , Humans , Selective Serotonin Reuptake Inhibitors/pharmacology , Autism Spectrum Disorder/drug therapy , Autism Spectrum Disorder/epidemiology , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Brain , Organoids
2.
Article in English | MEDLINE | ID: mdl-25423640

ABSTRACT

BACKGROUND AND OBJECTIVE: To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS: Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS: All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION: IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.


Subject(s)
Angiogenesis Inhibitors/toxicity , Receptors, Vascular Endothelial Growth Factor/toxicity , Recombinant Fusion Proteins/toxicity , Retina/drug effects , Retinal Pigment Epithelium/drug effects , Animals , Cell Line , Cell Survival , Drug Evaluation, Preclinical , Electroretinography , Humans , Intravitreal Injections , Male , Microscopy, Electron, Transmission , Ophthalmoscopy , Osmolar Concentration , Rabbits , Retina/physiopathology , Retinal Pigment Epithelium/ultrastructure , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors
SELECTION OF CITATIONS
SEARCH DETAIL
...