EDITOR'S PICK: Cheer up: a view of how fatty foods makes you feel less sad
It is well known that there is an intimate relationship between emotional state and food intake — we choose chocolate over an apple when overworked and stressed and comfort food makes us feel better. A team of researchers, led by Lukas Van Oudenhove, at the University of Leuven, Belgium, has now imaged changes in the brain when healthy nonobese individuals experience sadness. The team found that administration of a fat solution to the stomach attenuated the behavioral and nerve cell responses to sad emotion. These data have clear implications for a wide range of disorders, including obesity, eating disorders, and depression. As noted by Giovanni Cizza and Kristina Rother, at The National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, in an accompanying commentary, these data bring to mind the well-known phrase "We are what we eat".
TITLE: Fatty acid–induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans
AUTHOR CONTACT:
Lukas Van Oudenhove
University of Leuven, Leuven, Belgium.
Phone: 3216330147; Fax: 3216345939; E-mail: lukas.vanoudenhove@med.kuleuven.be.
View this article at: http://www.jci.org/articles/view/46380?key=d4c77fedce32ebbd4d8a
ACCOMPANYING COMMENTARY
TITLE: Was Feuerbach right: are we what we eat?
AUTHOR CONTACT:
Giovanni Cizza
The National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Phone: 301.496.8711; Fax: 301.480.2047; E-mail: cizzag@intra.niddk.nih.gov.
View this article at: http://www.jci.org/articles/view/58595?key=1e3fcd2605d3b5bc4b37
EDITOR'S PICK: New insight into a therapeutic approach to treating SMA
Spinal muscular atrophy (SMA) is the most frequently inherited cause of infant mortality. Two independent research groups — one led by Alex MacKenzie, at Children's Hospital of Eastern Ontario Research Institute, Ottawa; and one led by Umrao R. Monani, at Columbia University Medical Center, New York, and Cathleen M. Lutz, at The Jackson Laboratory, Bar Harbor — have now generated new data in mouse models of severe SMA that provide hope that a therapeutic providing meaningful benefit to individuals with SMA can be developed.
SMA is caused by mutations in the SMN1 gene that reduce levels of SMN protein, leading to loss of nerve cells in the brain stem and spinal cord that control muscles. This, in turn, leads to skeletal muscle weakness, wasting, and premature death. Increasing levels of SMN protein in individuals with SMA is considered a viable therapeutic option.
In the first study, MacKenzie and colleagues find that prolactin treatment increases SMN levels, improves muscle movement, and enhances survival in a mouse model of severe SMA. As prolactin has been used in the clinic to augment lactation in mothers of preterm infants, this drug has more immediate therapeutic potential than other drugs that do the same but have no history of safety in humans.
In the second study, Monani, Lutz, and colleagues find that increasing levels of SMN protein after disease onset in a mouse model of severe SMA has therapeutic benefit. These data raise the possibility that treatments designed to increase SMN levels could be effective, even if initiated at relatively advanced stages of the disease.
Kathryn Swoboda, at the University of Utah, Salt Lake City, discusses in detail these two reports and their therapeutic implications in an accompanying commentary.
TITLE: Prolactin increases SMN expression and survival in a mouse model of severe spinal muscular atrophy via the STAT5 pathway
AUTHOR CONTACT:
Alex MacKenzie
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Phone: 613.737.2772; Fax: 613.738.4833; E-mail: mackenzie@cheo.on.ca.
View this article at: http://www.jci.org/articles/view/46276?key=94a2a5d125f99c52847c
ACCOMPANYING ARTICLE
TITLE: Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy
AUTHOR CONTACT:
Umrao R. Monani
Columbia University Medical Center, New York, New York, USA.
Phone: 212.342.5132; Fax: 212.342.4512; E-mail: um2105@columbia.edu.
Cathleen M. Lutz
The Jackson Laboratory, Bar Harbor, Maine, USA.
Phone: 207.288.6341; Fax: 207.288.6665; E-mail: cat.lutz@jax.org.
View this article at: http://www.jci.org/articles/view/57291?key=d25d5e76ad0db01e3637
ACCOMPANYING COMMENTARY
TITLE: Of SMN in mice and men: a therapeutic opportunity
AUTHOR CONTACT:
Kathryn J. Swoboda
University of Utah, Salt Lake City, Utah, USA.
Phone: 801.585.9717; Fax: 801.587.9346; E-mail: swoboda@genetics.utah.edu.
View this article at: http://www.jci.org/articles/view/58752?key=ac37ad7fc13d2aa6c04e
VACCINES: Quantity of immune response key to flu vaccine efficacy in the elderly
The elderly and the very young are the individuals most at risk of the severe complications of flu, which include hospitalization and death. Vaccination effectively protects children and young adults against infection with the causative virus (influenza virus) but has limited efficacy in elderly individuals. This has been linked to an impaired ability of the vaccine to induce the immune system of elderly individuals to make an effective influenza virus–targeting antibody response. But whether this is due to decreases in the quantity and/or the quality of the antibodies produced is unclear. However, a team of researchers — led by Patrick Wilson, at the University of Chicago, Chicago; and Xiao-Song He, at Stanford University School of Medicine, Stanford — has now answered this question, it is down to decreased production of influenza virus–targeting antibodies. As Bonnie Blomberg and Daniela Frasca, at the University of Miami Miller School of Medicine, Miami, note in an accompany commentary, these data provide insight into what needs to be done to enhance the success of influenza vaccination in the elderly.
TITLE: Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
AUTHOR CONTACT:
Patrick C. Wilson
University of Chicago, Chicago, Illinois, USA.
Phone: 773.702.9009; Fax: 773.702.1576; E-mail: wilsonp@uchicago.edu.
Xiao-Song He
Stanford University School of Medicine, Stanford, California, USA.
Phone: 650.493.5000, ext. 66135; Fax: 650.852.3259; E-mail: xiaosong@stanford.edu.
View this article at: http://www.jci.org/articles/view/57834?key=c9479a5a3d20e31bd84f
ACCOMPANYING COMMENTARY
TITLE: Quantity, not quality, of antibody response decreased in the elderly
AUTHOR CONTACT:
Bonnie B. Blomberg
University of Miami Miller School of Medicine, Miami, Florida, USA.
Phone: 305.243.6040; Fax: 305.243.4623; E-mail: Bblomber@med.miami.edu.
View this article at: http://www.jci.org/articles/view/58406?key=bbcfbbfcfb51f14f328e
CARDIOLOGY: Setting the pace for a new therapeutic target for a common heart condition
A pacemaker is a small device that is placed in the chest or abdomen to help control an abnormal heart rate. In the United States, approximately $2 billion is spent each year on surgical implantation of a pacemaker in individuals with severe sinoatrial node dysfunction (SND), a common condition characterized by slower than normal heartbeats and long pauses between heartbeats that is associated with aging, heart failure, and high blood pressure. A team of researchers — led by Mark Anderson and Thomas Hund, at Carver College of Medicine, University of Iowa, Iowa City — has now generated in mice new insight into the molecular and cellular mechanisms that cause SND, providing a potential new therapeutic target for this condition. Specifically, the data suggest that targeting the protein CaMKII could prevent the development of SND in patients at high risk for the condition.
In an accompanying commentary, Björn C. Knollmann and Sabine Huke, at Vanderbilt University School of Medicine, Nashville, discuss in detail the molecular mechanism leading to SND uncovered by Anderson, Hund, and colleagues and how the work provides a clear target for developing new treatments aimed at preventing SND.
TITLE: Oxidized CaMKII causes cardiac sinus node dysfunction in mice
AUTHOR CONTACT:
Mark E. Anderson
Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Phone: 319.356.2745; Fax: 319.356.8608; E-mail: mark-e-anderson@uiowa.edu.
Thomas J. Hund
Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio, USA.
Phone: 614.247.7766; Fax: 614.247.7799; E-mail: Thomas.Hund@osumc.edu.
View this article at: http://www.jci.org/articles/view/57833?key=b44c0d59a49fa44fefe6
ACCOMPANYING COMMENTARY
TITLE: Oxidized CaMKII: a "heart stopper" for the sinus node?
AUTHOR CONTACT:
Björn C. Knollmann
Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Phone: 615.343.6493; Fax: 615.343.4522; E-mail: bjorn.knollmann@vanderbilt.edu.
View this article at: http://www.jci.org/articles/view/58389?key=fda9569f0d5be3b21477
NEUROBIOLOGY: Nothing is as simple as it seems: oh so true for a potential Huntington disease therapy
Huntington disease (HD) is an inherited neurodegenerative disorder. It is a devastating condition in which patients suffer from movement disorders, personality changes, cognitive impairment, and irreversible weight loss over the course of 15 years before death. Currently, there is no treatment that can stop or reverse the course of HD. It has been suggested that small-molecule drugs that trigger the heat shock response — a highly conserved protective mechanism that enables cells to withstand environmental stressors that promote protein misfolding and aggregation — could provide therapeutic benefit. However, a team of researchers, led by Gillian Bates, at King's College London, United Kingdom, has now found that this therapeutic approach is unlikely to be effective alone.
Bates and colleagues found that although activation of the HSR provided therapeutic benefit in a mouse model of HD, the beneficial effects were transient and diminished with disease progression. Further analysis identified the underlying mechanism for the transient nature of the benefit, leading James Shorter and Meredith Jackrel, at the University of Pennsylvania, Philadelphia, to suggest in an accompanying commentary that combination therapies that simultaneously unleash the HSR and prevent its impairment are likely to be needed if this approach is to be of benefit to individuals with HD.
TITLE: Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease
AUTHOR CONTACT:
Gillian P. Bates
King's College London, London, United Kingdom.
Phone: 44.20.7188.3722; Fax: 44.20.7188.2585; E-mail: gillian.bates@kcl.ac.uk.
View this article at: http://www.jci.org/articles/view/57413?key=0af1bbe2991b92b7dabc
ACCOMPANYING COMMENTARY
TITLE: Shock and awe: unleashing the heat shock response to treat Huntington disease
AUTHOR CONTACT:
James Shorter
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215.573.4256; Fax: 215.573.7290; E-mail: jshorter@mail.med.upenn.edu.
View this article at: http://www.jci.org/articles/view/59190?key=c41470a19fd3712ecacd
NEUROBIOLOGY: Nonmovement-related symptom of Parkinson disease explained
Parkinson disease (PD) is a relatively common neurodegenerative disorder. Its hallmark symptoms are tremors, muscular stiffness, postural instability, and slowness of movement. There are, however, other symptoms, which do not affect movement. These include depression, dementia, and failure of at least one component of the autonomic nervous system (the network of nerves that controls functioning below the level of consciousness, e.g., the heart rate and breathing rate). David Goldstein and colleagues, at The National Institute of Neurological Disorders and Stroke, Bethesda, have now gained new insight into the reason that autonomic nervous system control of the heart is dysfunctional in a subset of patients with PD. They hope that these data will help provide new approaches to diagnosis, treatment, and prevention.
TITLE: Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases
AUTHOR CONTACT:
David S. Goldstein
The National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
Phone: 301.496.2103; Fax: 301.402.0180. E-mail: goldsteind@ninds.nih.gov.
View this article at: http://www.jci.org/articles/view/45803?key=f0a69a95d1d7725a5e72
Journal
Journal of Clinical Investigation