Tuesday, November 11, 2008

BDNF and depression

Back in March I wrote a little bit about the convoluted relationships among stress, learning, and memory (here). About the same time, I wrote about the relationship between memory and an important neural growth factor, BDNF (here).

It seems that BDNF is an important bridge connecting the topics of memory, stress, and depression. Back in March I also started to write more about how BDNF is linked to depression, but I got sidetracked. So the rest of this message is what I started to write about that connection, which is why the research covered is from March or earlier.

But before turning to that, it should be noted that there is more to say about the relationship between BDNF and stress, which I'll put off a little longer. There's also more to say about the relationship between BDNF and antidepressant drugs, some of which is more recent than March. I'll put that off too.

So let's just get into the older stuff about BDNF and depression, to start the ball rolling again.

Research has shown that one way in which BDNF is linked to depression is through the neurotransmitter serotonin – whose connection to mood, depression, anxiety, etc. is pretty well known (think Prozac).

In particular, BDNF seems to affect expression of the gene for the serotonin transporter (SERT). (The gene itself is called SLC6A4, which stands for "solute carrier family 6, member 4".) SERT is a cell membrane protein that transports serotonin from the synapse between neurons back into the neuron from whence it came – enabling "serotonin reuptake". Some forms of the gene for SERT seem to predispose individuals who carry it to mood disorder.

Here are some reports of recent research on BDNF, which give an idea of the variety of effects it has within the nervous system. (The summaries included here are mine.)

The yin and yang of genes for mood disorders (3/12/08)
This research studied conditions under which a variant of the gene for SERT (i. e. SLC6A4) predisposes the carrier to mood disorders. Apparently there are also at least two variants of the gene for BDNF. An individual with one form of BDNF is particularly susceptible to the deleterious form of the SERT gene, but with the other form of BDNF, an individual is completely protected against it.

Brain Chemistry Ties Anxiety And Alcoholism (3/4/08)
Production of BDNF is known to be stimulated by exposure to alcohol. The researchers in this study, whose leader author is Subhash Pandey, also knew from previous experiments that reduced levels of BDNF in the amygdalas of normal laboratory rats led to increased anxiety in the rats, followed by increased consumption of alcohol. The question was what happened due to deficiency of BDNF that increased anxiety, and how did consumption of alcohol reverse this effect by restoring BDNF.

It is also known that BDNF stimulate the production of another protein, Arc. If Arc could be suppressed in the amygdala even in the presence of normal levels of BDNF, and the rats experienced increased anxiety anyhow, this would show that it is probably a deficiency of Arc rather than of BDNF that is responsible for the anxiety. And indeed, when Arc was suppressed in spite or normal BDNF, the rats had higher anxiety. They also consumed more alcohol. But when Arc levels returned to normal, the anxiety returned to normal, and alcohol consumption did too.

The question then came down to how a deficiency of Arc increased anxiety. It was found that temporarily reduced levels of Arc resulted in reduced numbers of dendritic spines of neurons in the amygdala. Since axons of other neurons form synapses with dendritic spines, there will be fewer synapses when there are fewer spines. At the same time, anxiety also increased. Conversely, when levels of Arc returned to normal, either naturally or as a result of higher levels of BDNF due to alcohol consumption, the number of spines increased, and anxiety decreased. Once Arc had increased normally, alcohol consumption decreased too.

Earlier results: Brain Chemical Plays Critical Role In Drinking And Anxiety (8/8/06) – when expression of BDNF (which is regulated by CREB) is blocked, anxiety and alcohol consumption in rats increases.

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