[14] BDNF is also expressed in the retina, kidneys, prostate, motor neurons, and skeletal muscle, and is also found in saliva.

[22] Certain types of physical exercise have been shown to markedly (threefold) increase BDNF synthesis in the human brain, a phenomenon which is partly responsible for exercise-induced neurogenesis and improvements in cognitive function.

TrkB autophosphorylation is dependent upon its ligand-specific association with BDNF,[10][11] a widely expressed activity-dependent neurotrophic factor that regulates plasticity and is dysregulated following hypoxic injury.

Promoter IV activity, leading to the translation of exon IV-containing mRNA, is strongly stimulated by calcium and is primarily under the control of a Cre regulatory component, suggesting a putative role for the transcription factor CREB and the source of BDNF's activity-dependent effects .

Through a protein signaling cascade requiring Erk, CaM KII/IV, PI3K, and PLC, NMDA receptor activation is capable of triggering BDNF exon IV transcription.

BDNF is released from the post-synaptic membrane in an activity-dependent manner, allowing it to act on local TrkB receptors and mediate effects that can lead to signaling cascades also involving Erk and CaM KII/IV.

[34][35] Both of these pathways probably involve calcium-mediated phosphorylation of CREB at Ser133, thus allowing it to interact with BDNF's Cre regulatory domain and upregulate transcription.

[37] NMDA receptor activation triggers the release of the regulatory inhibitor, allowing for BDNF exon IV upregulation to take place in response to the activity-initiated calcium influx.

The calcium influx triggered through NMDA receptors can lead to expression of BDNF, as well as other genes thought to be involved in LTP, dendritogenesis, and synaptic stabilization.

This has been shown to be important for processes such as spatial memory in the hippocampus, demonstrating the therapeutic and functional relevance of BDNF-mediated NMDA receptor activation.

BDNF is capable of increasing the mRNA expression of GluR1 and GluR2 through its interaction with the TrkB receptor and promoting the synaptic localization of GluR1 via PKC- and CaMKII-mediated Ser-831 phosphorylation.

[56] BDNF significantly enhanced the activation of GluR1 through phosphorylation of tyrosine830, an effect that was abolished in either the presence of a specific NR2B antagonist or a trk receptor tyrosine kinase inhibitor.

[56] Thus, it appears BDNF can upregulate the expression and synaptic localization of AMPA receptors, as well as enhance their activity through its postsynaptic interactions with the NR2B subunit.

This suggests BDNF is not only capable of initiating synapse formation through its effects on NMDA receptor activity, but it can also support the regular every-day signaling necessary for stable memory function.

One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing GABAergic signaling activities.

[clarification needed] Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions in spontaneous action potential frequencies that were mediated by an increase in the amplitude of GABAergic inhibitory postsynaptic currents (IPSC).

[61] In post-synaptic neurons they can influence dendritic spine formation and retraction as well as AMPA receptor insertion and removal.

[61] At their C-terminus, adducins possess a myristoylated alanine-rich C kinase substrate (MARCKS) domain which regulates their capping activity.

[62] PSD-95 localizes the actin-remodeling GTPases, Rac and Rho, to synapses through the binding of its PDZ domain to kalirin, increasing the number and size of spines.

[32][65] Preliminary research has focused on the possible links between BDNF and clinical conditions, such as depression,[66] schizophrenia,[67] and Alzheimer's disease.

[69] It has been shown that BDNF mRNA levels are decreased in cortical layers IV and V of the dorsolateral prefrontal cortex of schizophrenic patients, an area associated with working memory.