In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
In this review, we identify the health benefits associated with physical activity (PA); address the physical activity and sedentary guidelines issued by public health scientists as well as children’s compliance to these guidelines; discuss the importance of motor skill acquisition during early childhood; and identify different settings that contribute to physical activity participation and strategies for improving PA in these settings. Results show that regular participation in PA during childhood has numerous immediate benefits, including positive changes in adiposity, skeletal health, psychological health, and cardiorespiratory fitness. Additionally, motor skill development during early childhood may have immediate health benefits as well as long-lasting effects in adulthood. Furthermore, the benefits of PA during childhood also appear to positively influence adult health outcomes, such as increased bone mineral density. Key environmental settings that have been shown to influence children’s PA behavior include child care, active commuting to and from school, school recess, school physical education, after-school programs, churches, medical settings, and the home environment. Recommendations for practitioners and researchers are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.