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Can Neurotrophin-3 Reduce Anxious Temperament?

Increasing levels of the molecule neurotrophin-3 in the brain can alter dispositional anxiety, the tendency to perceive many situations as threatening, in nonhuman primates, researchers from the University of California, Davis, and the University of Wisconsin-Madison have found[1]. The molecule, neurotrophin-3, stimulates neurons to grow and make new connections.

Hang on a minute though.

Before you rush off in search of a supplement to fix your brain chemistry, you should know that neurotrophin-3 doesn’t come from any dietary intake of food. It is produced inside the body.

More about that later.

This finding does, however, provide hope for new strategies aimed at intervening early in life to treat people at risk for anxiety disorders, depression and related substance abuse. Current treatments work for only a subset of people and often only partially relieve symptoms.

Anxiety Disorders

Anxiety disorders typically develop around adolescence and can persist in affecting people for most of their lives. Currently, researchers can identify children who display an extreme anxious or inhibited temperament; these young people are at risk to develop stress-related psychopathologies such as anxiety disorders and depression as they transition to adulthood.

The roots of the study lie in research done by the group about eight years ago in preadolescent rhesus macaques, when researchers got their first peek at molecular alterations in the dorsal amygdala, a brain region important in emotional responses.

The authors speculated that altered processes in this region might underlie early-life anxiety.

Since then, the research team sequenced RNA from the dorsal amygdala to identify molecules related to dispositional anxiety and dorsal amygdala function. They eventually narrowed the potential molecules and selected neurotrophin-3, a growth factor, for further study.

The researchers then used an altered virus to boost levels of neurotrophin-3 in the dorsal amygdala of juvenile rhesus macaques. They found that the increase of neurotrophin-3 in the dorsal amygdala lead to a decrease in anxiety-related behaviors, particularly behaviors associated with inhibition, a core feature of the early-life risk for developing anxiety disorders in humans.

Subsequent brain imaging studies of these animals found that neurotrophin-3 changed activity throughout the distributed brain regions that contribute to anxiety.

Neurotrophins

Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their roles in the mammalian nervous system. They include brain- derived neurotrophic factor (BDNF), neurotrophin-4/5 (NT-4/5), neurotrophin-3 (NT-3), and nerve growth factor (NGF). Although originally discovered in the nervous system, many members of the neurotrophin family are expressed in a variety of nonneuronal systems including the cardiovascular, immune, endocrine, and reproductive systems[4].

So getting exercise[2] , eating healthy, and getting lots of sleep may help.

Also, there is good evidence that BDNF is boosted by intermittent fasting.[3]

Neurotrophin-3 (NT-3), itself is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor that has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses[5].

Fox hopes that other scientists can build on their research as an example of the kind of “deep science” that can transform how we understand psychopathology. The team has included a list of additional promising molecules that may warrant future investigation.

“We’re only just beginning. Neurotrophin-3 is the first molecule that we’ve been able to show in a non-human primate to be causally related to anxiety. It’s one of potentially many molecules that could have this affect. There could be hundreds or even thousands more,”

said Fox.

[1] Fox, Andrew S. et al. Dorsal Amygdala Neurotrophin-3 Decreases Anxious Temperament in Primates. Biological Psychiatry. DOI: https://doi.org/10.1016/j.biopsych.2019.06.022

[2] ZheYing, et al. Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord. Brain Research
Volume 987, Issue 1, 10 October 2003, Pages 93-99

[3] Mattson MP. Energy intake, meal frequency, and health: a neurobiological perspective. Annu Rev Nutr. 2005;25:237-60.

[4] Hempstead BL (February 2006). Dissecting the diverse actions of pro- and mature neurotrophins. Current Alzheimer Research. 3 (1): 19–24. doi:10.2174/15672050677569706

[5] Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R, Yancopoulos G (1990). Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 247 (4949 Pt 1): 1446–51. doi:10.1126/science.2321006