Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior

Area of Science:

• Neuroscience
• Molecular Psychiatry
• Behavioral Neuroscience

Background:

• Stressful life events contribute to mood disorders, but underlying mechanisms remain unclear.
• Brain-Derived Neurotrophic Factor (BDNF) influences mood, while its precursor (proBDNF) may have opposing effects.
• The roles of proBDNF co-receptors, P75(NTR) and sortilin, in mood regulation are largely unestablished.

Purpose of the Study:

• To investigate the role of sortilin in regulating mood-related behaviors in mice.
• To determine sortilin's involvement in proBDNF-mediated mood abnormalities.

Main Methods:

• Western blot analysis to quantify sortilin levels in stressed mice.
• Behavioral tests including open field, forced swimming, elevated plus maze, and Morris water maze.
• Assessment of mature BDNF and proBDNF levels in sortilin-deficient mice (in vivo and in vitro).

Main Results:

• Sortilin was upregulated in the neocortex and hippocampus of chronically stressed mice, correlating with decreased mobility and increased depression-like behavior.
• Sortilin deficiency led to hyperlocomotion and increased anxiety-like behavior but did not affect depression-like behavior or spatial cognition.
• ProBDNF administration induced depression-like behavior in both wild-type and sortilin-deficient mice, independent of sortilin levels.

Conclusions:

• Sortilin acts as a negative regulator of mood-related behaviors.
• Sortilin deficiency alters anxiety and locomotion but not depression or cognition.
• Sortilin represents a potential therapeutic target for mood disorder treatment.