Motor learning deficits and striatal GSK-3 hyperactivity in Akt3 knockout mice

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• The Akt protein kinase family (Akt1, Akt2, Akt3) are serine/threonine kinases involved in central nervous system functions.
• Akt kinases interact with molecular targets, including glycogen synthase kinase 3 (GSK-3).
• Akt3 is highly expressed in the brain, suggesting a specific role in neural processes.

Purpose of the Study:

• To investigate the role of the Akt3/GSK-3 pathway in the learning of complex motor skills.
• To determine if Akt3 deficiency impacts motor learning performance.

Main Methods:

• Utilized the accelerating rotarod task to assess motor learning in mouse models.
• Genetically deleted GSK-3α, GSK-3β, or Akt3 in mice.
• Performed biochemical analyses in the striatum.
• Administered chronic lithium treatment to Akt3-deficient mice.

Main Results:

• Genetic deletion of GSK-3α or GSK-3β did not affect rotarod performance.
• Akt3 deletion significantly impaired rotarod learning compared to wild-type mice.
• Akt3 deficiency led to altered levels of phosphorylated GSK-3 and tau, indicating increased GSK-3 activity.
• Lithium treatment prevented both biochemical and motor learning deficits in Akt3-deficient mice.

Conclusions:

• The Akt3/GSK-3 pathway is essential for the acquisition of new complex motor skills.
• Akt3 plays a critical role in regulating GSK-3 activity during motor learning.
• Targeting the Akt3-GSK-3 interaction may offer therapeutic potential for motor learning deficits.