BDNF

BDNF (brain-derived neurotrophic factor) is a small secreted protein of the neurotrophin family, and its role in the brain is to keep neurons alive and to strengthen the connections between them — the molecular basis of learning, memory formation, and mood regulation. It is most abundant in the hippocampus and cortex, the regions most involved in memory and executive function.

How it works

BDNF is made as a precursor, proBDNF, and cleaved into the mature form. The two have opposing effects, which is a recurring source of confusion:

• Mature BDNF binds the TrkB receptor, activating the PI3K/Akt, MAPK/ERK, and PLCγ pathways. The result is neuron survival, dendritic branching, and stronger synapses.
• proBDNF binds the p75 receptor and promotes synaptic weakening and pruning.

Release is activity-dependent: neurons that fire release BDNF, which strengthens exactly the synapses that were active. This makes BDNF a mechanical link between use and long-term potentiation, the cellular model of memory.

Role in the brain

Plasticity and memory. Blocking BDNF or TrkB impairs long-term potentiation in the hippocampus and impairs learning in animal models.

Neurogenesis. BDNF supports the survival of new neurons in the adult dentate gyrus.

Mood. Hippocampal BDNF is reduced in animal models of chronic stress and rises with several antidepressant treatments — the neurotrophic hypothesis of depression. It is a well-supported correlation, but not a demonstrated single cause.

Ageing and disease. Lower BDNF is reported in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. A common genetic variant (Val66Met) reduces activity-dependent release and is associated with measurable differences in memory performance.

What raises it

Aerobic exercise is the most reproducible intervention in humans, raising circulating BDNF acutely and with training. Sleep, dietary energy restriction, and enriched environments raise it in animal work. Chronic stress, chronic inflammation, and sleep restriction lower it.

Why peptides care

• Semax is an ACTH(4–10) analog reported to raise BDNF without the corticosteroid-releasing activity of the full hormone. It is registered as a medicine in Russia and holds no FDA or EMA approval.
• Selank is described as a neuroactive peptide that enhances BDNF signalling, a pathway central to neuroplasticity. The evidence for this is preclinical.

Neither compound is approved in the United States or the European Union, and human data on BDNF outcomes are limited. See each article for its evidence grades.