Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Recent Arctic amplification and extreme mid-latitude weather

The Arctic region has warmed more than twice as fast as the global average — a phenomenon known as Arctic amplification. The rapid Arctic warming has contributed to dramatic melting of Arctic sea ice and spring snow cover, at a pace greater than that simulated by climate models. These profound changes to the Arctic system have coincided with a period of ostensibly more frequent extreme weather events across the Northern Hemisphere mid-latitudes, including severe winters. The possibility of a link between Arctic change and mid-latitude weather has spurred research activities that reveal three potential dynamical pathways linking Arctic amplification to mid-latitude weather: changes in storm tracks, the jet stream, and planetary waves and their associated energy propagation. Through changes in these key atmospheric features, it is possible, in principle, for sea ice and snow cover to jointly influence mid-latitude weather. However, because of incomplete knowledge of how high-latitude climate change influences these phenomena, combined with sparse and short data records, and imperfect models, large uncertainties regarding the magnitude of such an influence remain. We conclude that improved process understanding, sustained and additional Arctic observations, and better coordinated modelling studies will be needed to advance our understanding of the influences on mid-latitude weather and extreme events

Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin

Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation in the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study was to replicate association of the rs4149056 variant in SLCO1B1 with severe statin-associated myopathy in a cohort of patients using a variety of statin medications and to investigate the association with specific statin types. We identified 25 cases of severe statin-associated myopathy and 84 controls matched for age, gender, statin type and dose. The rs4149056 variant in SLCO1B1 was not significantly associated with myopathy in this group as a whole. However, when subjects were stratified by statin type, the SLCO1B1 rs4149056 genotype was significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin. The Pharmacogenomics Journal (2012) 12, 233-237; doi: 10.1038/tpj.2010.92; published online 18 January 201