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Using brain surgery, specific areas in the brain can be stimulated with electrical impulses to reversibly change their activity and alleviate symptoms related to mental illnesses. This so-called deep brain stimulation and other methodological advances that even more selectively activate specific groups of neurons can give us clues as to what neural circuitry is involved in a particular mental disorder and whether therapeutic activation of these brain areas and neurons may be effective. In 'Bedside to Bench', Eric Nestler discusses two trials of individuals with anorexia nervosa in which deep brain stimulation of different brain areas resulted in improvement of behavioral domains associated with the syndrome. The results and potential of this technique in animals and humans may bring us closer to understanding the neurobiology of anorexia nervosa, which still remains a mystery and poses a challenge for treatment. In 'Bench to Bedside', Jennifer Warner-Schmidt peruses recent findings that uncover the functional connectivity of brain regions involved in depression and how activation of cortical regions can result in antidepressant effects that can compensate for the malfunction of other brain circuits that results in depression.

The Center for Biosecurity of the University of Pittsburgh Medical Center (UPMC) was recently renamed the UPMC Center for Health Security. As director and chief executive officer for the past four years, Tom Inglesby has expanded the center’s focus toward preventing public health crises arising from infectious diseases, pandemics and major natural disasters, in addition to biological, chemical and nuclear accidents or threats. Inglesby spoke with Kevin Jiang about how responses to bioterrorism, pandemics and natural disasters aren’t all that different.

Malaria remains the most deadly human parasitic disease. A new study finds that malaria parasites signal to mast cells to promote disease through the expansion of specialist dendritic cells and the subsequent activation of pathogenic CD8⁺ T cells (pages 730–738).

Anticancer cytotoxic drugs also kill normal progenitors found in rapidly regenerating tissues, resulting in prolonged hematopoietic insufficiency. Chemotherapy-induced toxicity of the nerves that regulate bone marrow niches required for regeneration of hematopoietic stem cells (HSCs) is involved in this insufficiency, which suggests that co-administration of neuroprotective agents may protect HSCs from the toxic effects of drugs such as cisplatin and vincristine (pages 695–703).

New insights into the actions of the hormone glucagon are provided by a recent study in rodents, which shows that glucagon can suppress hepatic glucose production by acting through the mediobasal hypothalamic region of the brain. This central regulatory mechanism is impaired in rats fed a high-fat diet, suggesting that hypothalamic glucagon resistance may be relevant to the hyperglycemia observed in obesity, diabetes or both (pages 766–772).

During resuscitation after cardiac arrest, a burst of reactive oxygen species (ROS) generated in mitochondria triggers a lethal cascade of events. Nitric oxide is known to be protective, but the mechanism is unknown. A new study shows that a mitochondria-targeted nitric oxide donor S-nitrosates the ND3 subunit of mitochondrial complex I, limiting its ability to generate ROS and protecting the heart against injury (pages 753–759).

Liver steatosis is a characteristic feature of hepatitis C virus (HCV) infection, and the virus itself is known to alter the lipid metabolism of infected hepatocytes. A recent study shows that HCV co-opts the antiviral innate immune response to stimulate the production of hepatic fat droplets, which it can then use to complete its own life cycle and spread (pages 722–729).

Blockage of transforming growth factor-β (TGF-β) signaling in subchondral bone after acute injury in rodents prevents aberrant bone remodeling and cartilage degeneration, suggesting that TGF-β signaling in bone may initiate osteoarthritis in some cases (pages 704–712).

Almost 50 years ago, the World Medical Association adopted the Declaration of Helsinki as an ethical guide for research involving human subjects. There are now proposed revisions under consideration that will provide additional protection for study participants as well as increased clarity regarding the responsibilities of those conducting the research. Making these changes is important in a complex environment where what is ethical is not always self-evident.

A recent plea by oncologists condemning inflated prices for some cancer drugs has ignited a debate on this topic between clinicians and pharmaceutical companies and highlights the need for a broader assessment of drug valuation.

Autism spectrum disorders (ASDs) are a clinically heterogeneous group of neurodevelopmental disorders characterized by social and communication deficits and repetitive behaviors. In a subset of individuals with ASD, mutations in genes involved in synaptic function have been identified, and this Perspective discusses the evidence from mouse models of ASD that synaptic deficits can be ameliorated in the mature brain. The authors also suggest a strategy for designing more informative clinical trials for ASD therapies that stratify patients according to their specific synaptic mutations.