Microbiome‐immune‐metabolic axis in the epidemic of childhood obesity: Evidence and opportunities

Obesity epidemic responsible for increase in diabetes, heart diseases, infections and cancer shows no signs of abating. Obesity in children is also on rise, indicating the urgent need of strategies for prevention and intervention that must begin in early life. While originally posited that obesity results from the simple concept of consuming more calories, or genetics, emerging research suggests that the bacteria living in our gut (gut microbiome) and its interactions with immune cells and metabolic organs including adipose tissues (microbiome‐immune‐metabolic axis) play significant role in obesity development in childhood. Specifically, abnormal changes (dysbiosis) in the gut microbiome, stimulation of inflammatory cytokines, and shifts in the metabolic functions of brown adipose tissue and the browning of white adipose tissue are associated with increased obesity. Many factors from as early as gestation appear to contribute in obesity, such as maternal health, diet, antibiotic use by mother and/or child, and birth and feeding methods. Herein, using evidence from animal and human studies, we discuss how these factors impact microbiome‐immune‐metabolic axis and cause obesity epidemic in children, and describe the gaps in knowledge that are warranted for future research.     

Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer's disease mouse model

Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid‐β protein, may underlie the observed neuronal loss. J. Comp. Neurol. 522:2319–2335, 2014. © 2014 Wiley Periodicals, Inc.