Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity

Area of Science:

• Neuroscience
• Endocrinology
• Molecular Biology

Background:

• Brain-derived neurotrophic factor (BDNF) is implicated in adult hypothalamic-pituitary-adrenal (HPA) axis regulation and homeostasis.
• The precise role of BDNF in HPA axis activity under basal and stress conditions requires further elucidation.

Purpose of the Study:

• To investigate the involvement of BDNF in HPA axis regulation under basal and stress conditions.
• To determine the effects of partial BDNF inhibition on HPA axis activity in rodents.

Main Methods:

• BDNF knockdown in adult male rats using stereotactic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle.
• Genetically induced BDNF knockdown (KD) in the central nervous system of mice during early development.
• Measurement of BDNF, adrenocorticotropic hormone (ACTH), and corticosterone levels.
• Assessment of HPA axis response to restraint stress.

Main Results:

• siRNA-induced BDNF knockdown in rats reduced BDNF levels in the hippocampus and hypothalamus, altering ACTH and corticosterone responses to stress.
• In mice, homozygous BDNF knockdown (60% reduction) significantly increased basal ACTH and corticosterone levels.
• Partial BDNF inhibition did not affect basal HPA axis activity in rats but required robust inhibition in mice.

Conclusions:

• A substantial endogenous BDNF pool is vital for basal HPA axis regulation.
• De novo BDNF synthesis plays a critical role in establishing an adapted HPA axis response to stress.
• BDNF is essential for both maintaining HPA axis homeostasis and adapting to stress.