Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain...

Area of Science:

• Neuroscience
• Neurobiology
• Behavioral Neuroscience

Background:

• Brain-derived neurotrophic factor (BDNF) influences central nervous system neurons, including serotonergic (5-HT) neurons.
• Previous studies were limited by the early lethality of BDNF null mice, hindering in vivo investigation of endogenous BDNF roles.

Purpose of the Study:

• To investigate the in vivo role of endogenous BDNF in the development and function of central 5-HT neurons using heterozygous BDNF(+/-) mice.
• To explore the relationship between BDNF levels, 5-HT system function, and associated behaviors.

Main Methods:

• Utilized heterozygous BDNF(+/-) mice with a normal lifespan.
• Assessed behavioral phenotypes (aggressiveness, hyperphagia, weight gain).
• Measured forebrain 5-HT levels, fiber density, c-fos induction after dexfenfluramine administration, and 5-HT receptor expression.

Main Results:

• BDNF(+/-) mice displayed enhanced intermale aggressiveness and hyperphagia with weight gain.
• Premature age-associated decrements in forebrain 5-HT levels and fiber density were observed.
• Blunted c-fos induction and altered 5-HT receptor expression indicated 5-HT dysfunction.

Conclusions:

• Endogenous BDNF is critical for normal development and function of central 5-HT neurons.
• BDNF deficiency leads to behavioral and neurochemical alterations linked to 5-HT dysfunction.
• BDNF(+/-) mice serve as a valuable model for studying psychiatric disorders involving serotonergic dysfunction.