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Anxiety Linked to Brain Chemical

§ May 14th, 2009 § Filed under brain research, depression, neuroscience, plasticity § No Comments

Scientists have linked low levels of a particular brain growth factor (fibroblast growth factor 2) to a disposition toward anxiety.  The University of Michigan study on rats appears in the May 13 issue of The Journal of Neuroscience. Since FGF2 increases the survival rate of new brain cells, the findings also highlight the role of neurogenesis, or cell birth and integration in the adult brain, in reducing anxiety. These findings may offer new possibilities for the treatment of anxiety and potentially depression.

Previous human studies led by the senior author, Huda Akil, PhD, at the University of Michigan and team at the Pritzker Consortium, showed that people with severe depression had low levels of FGF2, but couldn’t say whether low FGF2 levels caused the disease or were caused by it.

Javier Perez, PhD, also at the University of Michigan, bred rats for high or low anxiety for over 19 generations. The researchers found lower FGF2 levels in rats bred for high anxiety compared to those bred for low anxiety.

The study also found that providing a more stimulating and interesting environment for the rats increased FGF2 levels and reduced anxiety.  They also found that FGF2 treatment alone reduced anxiety behaviors in the high-anxiety rats.

“We have discovered that FGF2 has two important new roles: it’s a genetic vulnerability factor for anxiety and a mediator for how the environment affects different individuals. This is surprising, as FGF2 and related molecules are known primarily for organizing the brain during development and repairing it after injury,” Perez said.

The findings further indicate that FGF2 may in part reduce anxiety because it increases the survival of new cells in the hippocampus. Previous research has suggested that depression decreases the production and incorporation of new brain cells (neurogenesis). High-anxiety rats produced the same number of new brain cells as low-anxiety rats, but more of these new cells died off. FGF2 treatment and environmental enrichment each restored brain cell survival.

“This discovery may pave the way for new, more specific treatments for anxiety that will not be based on sedation — like currently prescribed drugs — but will instead fight the real cause of the disease,” said Pier Vincenzo Piazza, MD, PhD, Director of the Neurocentre Magendie an INSERM/University of Bordeaux institution in France, an expert on the role of neurogenesis in addiction and anxiety (not involved in the current study).

Brain Cell Growth And Mental Disorders

§ March 20th, 2009 § Filed under brain research, depression, neuroscience § No Comments

A new study in “Cell” connects the mechanism that produces new brain cells in adults with the incidence of schizophrenia and other neuropsychiatric disorders. The study, supports a controversial theory linking diseases such as schizophrenia and depression to neurogenesis and provides new avenues for the possible treatment of such conditions.

Image: flicker/Staurland

“This is the first time anybody has ever shown that this protein [coded by the gene] directly regulates the number of neural progenitors,” said Li-Huei Tsai, the study’s main author and a neuroscientist at the Picower Institute of Learning and Memory at the Massachusetts Institute of Technology.

Prior studies linked disturbances in neurogenesis in a brain region called the hippocampus to schizophrenia and suggested that anti-depressant medications such as Prozac work by stimulating hippocampal neurogenesis. The new findings link the gene, DISC1, to a signal pathway that controls neurogenesis and the development of the nervous system.

“It really fits in with a lot of background information to suggest that hippocampal neurogenesis in particular is potentially a process which is going wrong in psychiatric illness,” said Ben Pickard, a medical geneticist at the University of Edinburgh (not involved in the study).

Researchers first connected DISC1 and psychiatric disorders in 2001 — a large Scottish family with a high incidence of schizophrenia and bipolar disorder had a significant disruption in the gene’s sequence. Tsai and others have since linked other mutations in the gene to psychiatric disorders.

Tsai and her colleagues showed that the DISC1 protein “inhibits the inhibition” of neurogenesis. A mutation in the gene therefore can lead to the undisturbed inhibition neuronal growth. In adult mice, blocking the action of the DISC1 protein resulted in the display of symptoms associated with schizophrenia and depression.

GSK3-beta is the molecular target of lithium, the most effective treatment available for bipolar disorder. Although the compound has been used for decades, how it works is largely unknown. Tsai’s findings suggest that lithium’s mechanism may involve stimulating neurogenesis. “One of the most exciting aspects of the study is the parallel between this one function and lithium,” said Tsai.

It may also provide a genetic means of predicting which patients will respond to lithium. This is “giving us clues as to why the medications might work in some people and not in others,” said David Porteous, a molecular geneticist also at the University of Edinburgh (also not involved in the present work, but coauthor of the original DISC1 family study). “It’s not just a very good piece of science; it’s also giving us a roadmap to what we should be doing next.”

“We’re starting to develop a kind of genetic network around the DISC1 pathway,” he said, which points to “targets for intervention in a much more rational fashion than what’s been possible.”

I’d add that it might also provide an interesting avenue for non-drug therapy using brain exercises that promote neurogenesis.

Other posts related to mental health and neurogenesis:

How exercise and brain exercise can help combat depression

More on Depression And Brain Exercise

Brain Plasticity And Chronic Stress

§ February 26th, 2009 § Filed under depression, plasticity § 1 Comment

As a reminder that plastic change can be harmful as well as helpful to our mental health, scientists have identified what looks to be a process of long term damage caused by chronic stress.

“Stress and depression are known to cause a reversible retraction of dendrites in certain brain cells, particularly in the hippocampus, that McEwen and colleagues refer to as “adaptive plasticity.” The new research suggests that an increase in KA1, caused by the corticosteroid response in rats, may trigger this retraction. The finding follows recent work by Rockefeller’s Sidney Strickland, head of the Laboratory of Neurobiology and Genetics, that showed that KA1 production explodes in the hippocampus during simulated stroke in mice, driving a cell-death cascade that begins when part of the brain is deprived of blood. Combined, the work suggests that the relatively understudied KA1 subunit plays an important role in a key area of the brain in both causing damage in an uncontrolled trauma such as a stroke and in protecting the brain from damage under the more controlled circumstances of chronic stress.

“McEwen and colleagues have shown that healthy brains are remarkably resilient in the face of stress — brains replace their retracted neurons once the stress is removed. Perhaps, the researchers say, the same will prove true for depression. “One of the great hopes is that these changes in the hippocampus that happen with prolonged depression may not be signs of permanent irreversible damage but they may actually be signs of plasticity that we can treat with appropriate medications and also behavioral therapies,” McEwen says.”

Why Aren’t We Learning to Rethink Drugs?

§ December 13th, 2008 § Filed under brain research, depression, neuroscience, plasticity § No Comments

When I saw an article in the MIT Technology Review called “Making an Old Brain Young: Scientists are developing new ways to manipulate the brain’s normal plasticity” I thought to myself “oh, good, more evidence of useful, natural therapies that can leverage plasticity.”

But the second sentence of the article begins “Drugs that target these mechanisms might eventually help treat neurological disorders …”

Not that the medical world shouldn’t be evaluating drugs that leverage plasticity. What concerned me about the article was the complete absence of reference to therapies that might not require drugs. Meanwhile, the Australian Alzheimer’s Association has endorsed brain training exercises as a non-pharmacalogical mechanism for delaying or preventing the onset of Alzheimer’s symptoms. The most effective therapies for stroke victims leverage plasticity through non-drug therapies. Progressive learning specialists are working with brain exercises to mitigate or correct learning dysfunctions. And other research has shown that the generation of new nerve cells in the dentate gyrus helps combat depression — something that can be assisted with exercise and brain exercise…

If our newfound knowledge of plasticity can teach us anything surely it should be teaching us that there are many remarkable alternatives to drugs.

Depression, Exercise And Brain Exercise

§ September 1st, 2008 § Filed under antidepressants, brain research, depression, neuroscience, plasticity § 2 Comments

Dentate Gyrus

Dentate Gyrus

Brain activity and neural response in the region of the brain known as the dentate gyrus has been tied to the symptoms and experience of depression. The dentate gyrus is also one of the few areas of the brain thought to be able to generate significant numbers of new brain cells in a process known as neurogenesis. This has led to research into the process of depression and the ways that we can combat persistent depression.

ScienceDaily reports on new research that Antidepressants Need New Nerve Cells To Be Effective. The study by researchers from UT Southwestern Medical Center showed that the effectiveness of anti-depressants in mice depended upon the growth of new nerves in the part of the brain called the dentate gyrus.

The next question of course becomes how to stimulate new nerve cell generation.

Dr. Luis Parada. (Credit: Image courtesy of UT Southwestern Medical Center)

Dr. Luis Parada. (Credit: Image courtesy of UT Southwestern Medical Center)

There are two: aerobic exercise and working-memory activation.

The dentate gyrus plays a key role in memory formation. Research has shown that stimulation of working-memory activates the dentate gyrus.

(Research subjects in working-memory training and users of Mind Sparke Brain Fitness Pro report greater levels of satisfaction and well-being; an intriguing link and another great reason to be brain-training.)