Nanoparticulate Brain-Derived Neurotrophic Factor (BDNF) as a Potential Antidepressant via Neuroendocrine Mechanisms in Experimental Model of Depression

Nur Amirah Diyana, Binti Razlan (2025) Nanoparticulate Brain-Derived Neurotrophic Factor (BDNF) as a Potential Antidepressant via Neuroendocrine Mechanisms in Experimental Model of Depression. Masters thesis, Universiti Malaysia Sarawak.

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Abstract

The hypothalamo-hypophyseal-adrenal axis (HHAA) links neurogenesis, neurotransmission, and immunoendocrine factors in depression. Stress-induced HHAA activation lowers brain-derived neurotrophic factor (BDNF) in the hippocampus, causing atrophic changes and depressive symptoms. Traditional antidepressants increase BDNF, but BDNF cannot cross the blood-brain barrier. Nanocarriers aid delivery, yet nano-BDNF’s potential remains underexplored. This study examines nano-BDNF’s antidepressant effects in mice. Thirty C57BL/6 mice were divided into five groups: normal control, depression model, negative control, fluoxetine-treated, and nano-BDNF-treated. Behavioral tests, ELISA, and histological analysis assessed reserpine-induced depression. Results showed nano-BDNF and fluoxetine reversed depression effects, but nano-BDNF was superior in restoring HHAA function and immune balance. Histology confirmed nano-BDNF reversed adrenal and thymic changes linked to depression-induced immunosuppression. This study identifies nano-BDNF with poloxamer 188 as a promising antidepressant, comparable to fluoxetine in behavior recovery but superior in restoring HHAA balance.

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