BDNF and major depressive disorder: Preclinical: With increased knowledge of the nose-brain pathway and IN therapeutics, IN-BDNF to mouse models of depression is being explored: in a chronic mild stress (CMS) induced-depression model, mice were given AAV-packaged BDNF fused with cell-penetrating peptides, human immunodeficiency virus-1 transactivator of transcription (TAT), and influenza A hemagglutinin glycoprotein 2 (HA2).