February 3, 2011

Aliquots — research highlights from VUMC laboratories


Paraplegia-causing proteins pair up

Hereditary spastic paraplegia (HSP), a group of progressive neurodegenerative disorders that impairs the ability to walk, can be caused by mutations in more than 40 different genes. Despite this genetic heterogeneity, the pathologic features – degeneration of long axons in the spinal cord – are relatively uniform, suggesting that dysfunction of a common biochemical pathway might contribute to HSP.

Peter Hedera, M.D., and colleagues explored whether two proteins implicated in HSP – atlastin-1 and NIPA1 – are part of a common pathway. They report in the January issue of Molecular and Cellular Neuroscience that atlastin-1 and NIPA1 bind to each other and that this interaction helps deliver atlastin-1 to the cell surface. They also show that HSP-causing mutations (in either atlastin-1 or NIPA1) alter the cellular distribution of the complex and reduce growth of axons and dendrites in cultured rat cortical neurons.

The findings support the idea that atlastin-1 and NIPA1 are members of a common biochemical pathway that supports axon maintenance, which could provide new therapeutic targets for HSP.

— Leigh MacMillan


Mapping obesity circuitry in brain



In the battle of the bulge, one important battalion is a set of brain cells expressing the melanocortin-4 receptor (MC4R). Via signals from the fat-derived hormone leptin, these neurons regulate feeding behavior and fat metabolism in an attempt to regulate body weight. But how leptin influences and acts on this brain circuitry is not fully understood. 

Using mice with fluorescently-tagged MC4R, Masoud Ghamari-Langroudi, Ph.D., Roger Cone, Ph.D., and colleagues analyzed how the activity of MC4R neurons of the paraventricular nucleus of the hypothalamus (PVN) are regulated by leptin and by metabolic state (i.e., fasting).

They report in the Jan. 4 Proceedings of the National Academy of Sciences that fasting increases firing of these neurons and that leptin administration returns the firing to normal levels. They also show that contrary to the conventional view that leptin indirectly regulates PVN neuron activity, it can also inhibit the activity of PVN neurons directly. Such details of the brain circuitry underlying energy balance could provide important clues to understanding – and combating – obesity.

— Melissa Marino


BPA exposure tests in question

The safety of industrial chemicals bisphenol A (BPA) and alkylphenols, which are used in commercial products like plastics, has recently been called into question. Exposure to these chemicals is typically measured by their excretion in urine, but impaired kidney function may make such measurements inaccurate.



To assess how kidney function influences urinary excretion of these compounds, Qi Dai, M.D., Ph.D., Chuan-Ming Hao, M.D., Ph.D., and colleagues calculated renal function in 2,573 adults without known kidney impairment. In Environmental Health Perspectives, they report that between 42.6 percent and 58.2 percent of subjects had mildly to significantly reduced renal function. Urinary excretion of triclosan (an alkylphenol), and possibly BPA, decreased with decreasing renal function. These associations differed by age and sex of the subject.

Whether the reduced urinary excretion indicates that the chemicals accumulate in the body or are metabolized through another pathway, the findings suggest that more study is needed to determine the value of these measures as biomarkers of exposure.

— Melissa Marino


Seeing serotonin neurons in action

Serotonin – a chemical that has roles in multiple brain functions, including mood, sleep and cognition – is manufactured by clusters of brainstem neurons gathered in the raphé nuclei. A reliable, non-invasive imaging method for assessing raphé neuron activity would be valuable for understanding serotonin signaling in depression and related conditions.

Using functional magnetic resonance imaging (fMRI) for raphé neurons has been challenging because of noise and artifacts. Now, Ronald Salomon, M.D., and colleagues have evaluated a different fMRI method (time-series analysis) to study raphé neurons.

They acquired fMRI scans in 11 patients after a control diet and after a diet that transiently diminishes serotonin (acute tryptophan depletion) to alter raphé neuron activity. Time-series fMRI revealed an increase in raphé fast oscillations during the tryptophan depletion diet and a decrease in connectivity of the raphé neurons to other brain areas. The findings, reported in Psychiatry Research: Neuroimaging, suggest that time-series fMRI may be useful for assessing raphé neuron function.

— Leigh MacMillan


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: aliquots@vanderbilt.edu.

Past Aliquots

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