Atlas of exercise-induced brain activation in mice.

Objectives: There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative diseases. In this study, we utilize forced treadmill running and distance-matched voluntary wheel running, coupled with light sheet 3D brain imaging and c-Fos immunohistochemistry, to generate a comprehensive atlas of exercise-induced brain activation in mice.

Methods: To investigate the effects of exercise on brain activity, we compared whole-brain activation profiles of mice subjected to treadmill running with mice subjected to distance-matched wheel running.

Uncovering CNS access of lipidated exendin-4 analogues by quantitative whole-brain 3D light sheet imaging.

Peptide-based drug development for CNS disorders is challenged by poor blood-brain barrier (BBB) penetrability of peptides. While acylation protractions (lipidation) have been successfully applied to increase circulating half-life of therapeutic peptides, little is known about the CNS accessibility of lipidated peptide drugs. Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method to visualize whole-brain 3D distribution of fluorescently labelled therapeutic peptides at single-cell resolution.

Multimodal 3D Mouse Brain Atlas Framework with the Skull-Derived Coordinate System.

Magnetic resonance imaging (MRI) and light-sheet fluorescence microscopy (LSFM) are technologies that enable non-disruptive 3-dimensional imaging of whole mouse brains. A combination of complementary information from both modalities is desirable for studying neuroscience in general, disease progression and drug efficacy. Although both technologies rely on atlas mapping for quantitative analyses, the translation of LSFM recorded data to MRI templates has been complicated by the morphological changes inflicted by tissue clearing and the enormous size of the raw data sets.

Digital Brain Maps and Virtual Neuroscience: An Emerging Role for Light-Sheet Fluorescence Microscopy in Drug Development.

The mammalian brain is by far the most advanced organ to have evolved and the underlying biology is extremely complex. However, with aging populations and sedentary lifestyles, the prevalence of neurological disorders is increasing around the world. Consequently, there is a dire need for technologies that can help researchers to better understand the complexity of the brain and thereby accelerate therapies for diseases with origin in the central nervous system.

Whole-brain activation signatures of weight-lowering drugs.

Objective: The development of effective anti-obesity therapeutics relies heavily on the ability to target specific brain homeostatic and hedonic mechanisms controlling body weight. To obtain further insight into neurocircuits recruited by anti-obesity drug treatment, the present study aimed to determine whole-brain activation signatures of six different weight-lowering drug classes.

Methods: Chow-fed C57BL/6J mice (n = 8 per group) received acute treatment with lorcaserin (7 mg/kg; i.

An Optimized Mouse Brain Atlas for Automated Mapping and Quantification of Neuronal Activity Using iDISCO+ and Light Sheet Fluorescence Microscopy.

In recent years, the combination of whole-brain immunolabelling, light sheet fluorescence microscopy (LSFM) and subsequent registration of data with a common reference atlas, has enabled 3D visualization and quantification of fluorescent markers or tracers in the adult mouse brain. Today, the common coordinate framework version 3 developed by the Allen's Institute of Brain Science (AIBS CCFv3), is widely used as the standard brain atlas for registration of LSFM data. However, the AIBS CCFv3 is based on histological processing and imaging modalities different from those used for LSFM imaging and consequently, the data differ in both tissue contrast and morphology.