BDNF

Where it comes from

Made in

Neurons of cortex and hippocampus, made and released by activity; also muscle, platelets and gut

Sent out by

Neuronal activity, learning, exercise and antidepressant treatment; stress and inflammation lower it

Acts on

• Synapses (strengthening and growth)
• Hippocampal neurons
• Sensory and motor neurons
• Hypothalamus (appetite)

What it does

• Strengthens synapses during learning and keeps neurons alive
• Mediates part of the benefit of exercise and of antidepressants on the brain
• Loss of one copy causes severe obesity; the common Val66Met variant alters its release and is studied in memory and mood

In medicine

• No medicine; blood BDNF is a research marker that is low in depression and rises with treatment
• Injected BDNF failed in ALS trials in the 1990s; it does not cross the blood-brain barrier and lasts minutes in blood ¹

Beyond the body’s own use

• The large trial that settled the injected form enrolled 1,135 patients with ALS on BDNF under the skin for nine months and missed its primary endpoints; the benefits reported afterwards came from subgroups chosen after the fact ¹
• Blood BDNF is a poor stand-in for the brain: a meta-analysis of exercise training found only a small rise in resting levels, and platelets carry far more of it than plasma does ³
• The common Val66Met variant changes how much a neuron releases on demand and has been studied in memory and mood for two decades without yielding a clinical use ²
• Small-molecule TrkB agonists and gene therapy delivered into the brain are the current early-stage approaches, taken because the protein itself cannot be given usefully from outside