behavioral neuroscience

So, more recently, we’ve discovered that my husband is most likely ADHD. He handles the concentration aspect well overall, so if he had it as a child, it was never picked up on. But we’re pretty sure he does have it, as well as major problems with executive dysfunction. He often forgets to eat, forgets chores, has trouble making decisions, and ends up thinking of himself as lazy.

Specific combinations of gut bacteria produce substances that affect myelin content and cause social avoidance behaviors in mice, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published in the medical journal eLife. This research suggests that targeting intestinal bacteria, or their metabolites, could be one way to treat debilitating psychiatric disorders and demyelinating diseases, like multiple sclerosis.

Multiple sclerosis is an autoimmune disorder characterized by damage to myelin, the insulating sheath around the axons of nerve cells that allows for faster electrical impulse conduction.  Myelination is critical for everyday brain function. Damaged myelin results in altered synaptic transmission and clinical symptoms. Previous research from the Center of Excellence for Myelin Repair at The Friedman Brain Institute at the Icahn School of Medicine reported a thinning of myelin and a reduction of myelinated fibers in preclinical models of depression, thereby providing a biological insight for the high rate of depression in MS patients.

This current study led by Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics, and Neurology, and Chief of the Center of Excellence for Myelin Repair, and post-doctoral fellow Mar Gacias, PhD, identifies bacteria-derived gut metabolites that can affect myelin content in the brains of mice and induce depression-like symptoms.  

Researchers transferred fecal bacteria from the gut of depressed mice to genetically distinct mice exhibiting non-depressed behavior. The study showed that the transfer of microbiota was sufficient to induce social withdrawal behaviors and change the expression of myelin genes and myelin content in the brains of the recipient mice.

“Our findings will help in the understanding of microbiota in modulating multiple sclerosis,” says Dr. Casaccia. “The study provides a proof of principle that gut metabolites have the ability to affect myelin content irrespective of the genetic makeup of mice. We are hopeful these metabolites can be targeted for potential future therapies.”

In an effort to define the mechanism of gut-brain communication, researchers identified bacterial communities associated with increased levels of cresol, a substance that has the ability to pass the blood-brain barrier. When the precursors of myelin-forming cells were cultured in a dish and exposed to cresol, they lost their ability to form myelin, thereby suggesting that a gut-derived metabolite impacted myelin formation in the brain.

(Image caption: Fluorescent labelling of the Tau protein in a hNT human cell. Credit: © Inserm / U837)

Modulation of brain cholesterol: a new line of research in Alzheimer’s disease treatment?

We have known for some years that Alzheimer’s disease is characterised by two types of lesions, amyloid plaques and degenerated tau protein. Cholesterol plays an important role in the physiopathology of this disease. Two French research teams (Inserm/CEA/University of Lille/University of Paris-Sud) have just shown, in a rodent model, that overexpressing an enzyme that can eliminate excess cholesterol from the brain may have a beneficial action on the tau component of the disease, and completely correct it. This is the first time that a direct relationship has been shown between the tau component of Alzheimer’s disease and cholesterol. This work is published in the 10 September 2015 issue of Human Molecular Genetics.

Excess brain cholesterol cannot freely cross the blood-brain barrier; to be eliminated it must be converted into 24-hydroxycholesterol (24-OHC) by the enzyme CYP46A1 (cholesterol-24-hydroxylase). At Inserm Unit 1169, Nathalie, Cartier, coordinator of this work, and Patrick Aubourg, director of the unit, proposed the hypothesis that increasing the efflux of cholesterol from the brain by overexpressing CYP46A1 might have a beneficial effect on the elements of Alzheimer pathology.

The first step in this work made it possible to show that injecting a viral vector, AAV-CYP46A1, effectively corrects a mouse model of amyloid pathology of the disease, the APP23 mouse. CYP46A1 thus appears to be a therapeutic target for Alzheimer’s disease.

Conversely, in vivo inhibition of CYP46A1 in the mice, using antisense RNA molecules delivered by an AAV vector administered to the hippocampus, induces an increase in the production of Aß peptides, abnormal tau protein, neuronal death and hippocampal atrophy, leading to memory problems. Together these elements reproduce a phenotype mimicking Alzheimer’s disease.

These results demonstrate the key role of cholesterol in the disease, and confirm the relevance of CYP46A1 as a potential therapeutic target (work published in Brain on 3 July 2015).

Taken together, this work now enables the research team coordinated by Nathalie Cartier, Inserm Research Director, to propose a gene therapy approach for Alzheimer’s disease: intracerebral administration of a vector, AAV-CYP46A1, in patients with early and severe forms (1% of patients, familial forms) for whom there is no available treatment.

Scientists Uncover Unique Role of Nerve Cells in the Body’s Use of Energy

While it is well-known that weight gain results from an imbalance between what we eat and our energy expenditure, what is not obvious is the role that the nervous system plays in controlling that energy balance. Now scientists from the Florida campus of The Scripps Research Institute (TSRI) have shed light on that question.

“Our new study has identified novel populations of nerve cells that regulate appetite, thermogenesis and physical activity,” said TSRI Professor Baoji Xu, who led the research. “We think these neurons could be targets for drug development.”

The findings were published by the journal Cell Metabolism online ahead of print on June 11.

In the new study, Xu and his colleagues examined several groups of neurons that express a substance called “brain-derived neurotrophic factor” (BDNF) within a small brain region called the paraventricular hypothalamus.

BDNF is an extremely important protein in the brain and is involved in a number of functions. It has been shown that deleting the BDNF gene causes significant problems, among them, dramatically increased appetite (hyperphagia) and severe obesity.

The new study shows that deleting the BDNF gene also impairs thermogenesis—the ability of cells to burn fat to produce heat. The study further reveals two distinct types of BDNF neurons—those that control appetite or satiety and those that control thermogenesis. Not only do these two groups play different biological roles, they are located in two separate sections of the paraventricular hypothalamus brain region.

This “geographical” split raises some interesting questions. “We don’t yet know what the distinctive placement means to the control of body weight, nor do we know if these two clusters of neurons communicate with each other as yet,” said Juanji An, the first author of the study and a member of the Xu lab. “But given the fact that mice and humans with mutations in the BDNF gene or its receptor develop severe obesity, a better understanding of the mechanism underlying the effect BDNF has on body weight could provide great insights into the regulation of energy balance.”

One of the most interesting and memorable finding that I learned from my cognitive psychology class was the influence of colors on our state of mind. Colors not only influence how we think, how we feel, but potentially how we behave.