August 11, 2011

Aliquots: Research highlights from VUMC laboratories


Focus of fear in Williams syndrome

Individuals with Williams syndrome (WS) are highly sociable and have little fear of strangers, but they often exhibit significant non-social fears. Abnormal function of the amygdala – a brain region involved in emotional processing – may play a role in these features, but it is unclear whether these abnormalities are specific to WS or are generally associated with traits like sociability and fearfulness.

Using functional MRI, Jennifer Blackford, Ph.D., and colleagues measured amygdala response to fear-inducing social and non-social images in WS compared to two control groups – individuals with high levels of non-social fear (inhibited temperament, or IT) and individuals with high sociability (uninhibited temperament, or UT). They found that the WS group had larger amygdala responses when viewing non-social fear images (e.g., spiders) compared to the IT group. However, their response to fearful social images was proportionate to their sociability.

The results, reported in the July Developmental Cognitive Neuroscience, suggest that heightened amygdala response to non-social fear is specific to WS.

— Melissa Marino

Heart attack repair kit

Myocardial infarction (MI) is the leading cause of death worldwide. Because current therapies do not repair damaged cardiac tissue, MI often leads to heart failure – an inability of the heart to meet the body’s blood flow needs.

Previous studies have suggested that the Wnt signaling pathway could be a therapeutic target to improve heart muscle repair after MI, but the results have been contradictory. To clarify the Wnt pathway’s role, Antonis Hatzopoulos, Ph.D., and colleagues examined Wnt signaling after an experimental MI in mouse models.

They report in the July issue of Disease Models & Mechanisms that a large number of Wnt-positive cells accumulate in the infarct area one week after MI. They also showed that MI triggers a cellular change called endothelial-to-mesenchymal transition (EndMT), and that Wnt signaling is active in EndMT-derived mesenchymal cells that take part in cardiac tissue repair after MI.

The findings could lead to new strategies to improve cardiac repair through manipulation of the Wnt signaling pathway.

— Leigh MacMillan

Depressed brains more stressed

The causes of major depression, one of the most common mental disorders in the United States, are still a mystery. To explore molecular changes associated with major depression, Richard Shelton, M.D., and colleagues examined gene expression in a particular brain region involved in reward-related behavior (Brodmann Area 10).

The researchers compared gene expression in post-mortem brain tissue samples from patients with a history of major depression – not taking medications that alter brain function at the time of death – with samples from matched normal controls. In addition to examining changes in the expression of single genes, the investigators used Gene Set Enrichment Analysis to determine the expression of sets of genes implicated in depression. The two approaches revealed altered expression of a large number of genes; in particular, they found increased expression of inflammatory molecules and factors associated with cell death (apoptosis).

The findings reported in the July issue of Molecular Psychiatry show evidence of inflammatory, apoptotic and oxidative stress in major depression.

— Leigh MacMillan

Two paths to prevent atherosclerosis?

Immune system cells called macrophages play a key role in atherosclerosis. In the artery wall, these cells take up lipoproteins and activate inflammatory responses. Two proteins, low-density lipoprotein receptor-related protein 1 (LRP1) and apolipoprotein E (apoE), are crucial to these processes and collaborate to control cholesterol trafficking, cell survival and disposition of damaged or dead cells in the arterial plaque.

Previously, Sergio Fazio, M.D., Ph.D., MacRae Linton, M.D., Patricia Yancey, Ph.D., and colleagues showed that deficiency of LRP1 in macrophages increased atherosclerosis despite reducing the intake of lipoproteins and increasing secretion of apoE. To determine whether the protective effect of LRP1 requires apoE, the researchers examined atherosclerosis development in mice lacking both macrophage LRP1 and apoE.

In the July 26 issue of Circulation, they report that macrophage LRP1 slows atherosclerosis development by regulating cell death and toning down inflammatory processes – and does so independently of its interaction with apoE. The results may inform the development of therapies to halt or reverse plaque formation.

— Melissa Marino

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012