Using 3D Organoid Cultures to Model Intestinal Physiology and Colorectal Cancer.

The three-dimensional (3D) structure of the intestine is a key determinant of differentiation and function; thus, preserving this architecture is an important consideration for studies of intestinal homeostasis and disease. Over the past decade, a number of systems for 3D intestinal organoid cultures have been developed and adapted to model a wide variety of biological phenomenon. PURPOSE OF THIS REVIEW: We discuss the current state of intestinal and colorectal cancer (CRC) 3D modeling, the most common methods for generating organoid cultures, and how these have yielded insights into intestinal physiology and tumor biology. RECENT FINDINGS: Organoids have been used to model numerous aspects of intestinal physiology and disease. Recent adaptations have further improved disease modeling and high-throughput therapeutic screening. SUMMARY: These studies show intestinal organoid models are a robust, highly tractable system which maintains many vital features of intestinal tissue, making them a pivotal step forward in the field of gastroenterology.

Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing.

Chronic circadian dysfunction impairs declarative memory in humans but has little effect in common rodent models of arrhythmia caused by clock gene knockouts or surgical ablation of the suprachiasmatic nucleus (SCN). An important problem overlooked in these translational models is that human dysrhythmia occurs while SCN circuitry is genetically and neurologically intact. Siberian hamsters (Phodopus sungorus) are particularly well suited for translational studies because they can be made arrhythmic by a one-time photic treatment that severely impairs spatial and recognition memory. We found that once animals are made arrhythmic, subsequent SCN ablation completely rescues memory processing. These data suggest that the inhibitory effects of a malfunctioning SCN on cognition require preservation of circuitry between the SCN and downstream targets that are lost when these connections are severed.